Vogt Belluscio Article Opt

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Aesth. Plast. Surg. 11:131-156, 1987 AestheucPlasncSurgery9 1987 Springer-Verlag New York Inc.

Controvers ies in P las t ic Surgery: Suct ion-Ass is ted Lipectomy (SAL) and theh C G ( H u m a n C h o r io n ic G o n a d o t r o p in ) P r o t o c o l fo r O b e s it y T r e a t m e n tTrudy Vogt, M.D. and Daniel Belluscio, M.D.Zfirich, Switzerland

Abs t r a c t . The advent o f SAL (suction-assisted lipectomy)h a s dramatically increased the number of obese patientscoming to our consultation offices. Despite several artic-les suggesting a conservative approach to fat suction,some reports insinuate that SAL might be a useful tool forobesity treatment. This hypothesis is refuted by a vastbody of evidence that concludes that the adipose tissuemay regenerate in adult humans. Therefore, surgical pro-cedures are not advised as the method of choice to man-age the disease. On the other hand, the terms obesity andbeing overweight may not be interchangeable. Obesitymay be a disease whereas being overweight is a sign ofth e disease. Consequently, proper preoperative selectionof candidates for SAL becomes mandatory. The hCG(human chorionic gonadotropin) method for obesity treat-ment appears to be a complete program for the manage-ment of obesity. It contains pharmacologic, dietetic, andbehavior modification aspects in a 40-day course of treat-ment. Some data suggest hCG to be lipolytic, thus ex-plaining former clinical observations regarding body fatredistribution in treated patients, hOG commercial prepa-rations contain fl-endorphin, an opioid peptide linked tomood behavior. This article speculates on the possibleactions of the complex hCG fl-endorphin in the neuromo-dulation of mood and energy metabolism. The methodcomprises a behavior modification that helps in handlingthe patient better. There are some correlations between acurrent behavior modification program and the basicguidelines contained in the hCG protocol. Thus, the hCGmethod appears to be a reasonable alternative in the man-agement of a long-standing, unsolved problem of humanmetabolism.K e y wo r ds : Adipose tissue - - Metabolism - - En-dorphins -- physiology - - Obesity, treatment -- Gonad-

Address reprint requests to Dr. Daniel Belluscio, Four-nier 2562, 1437 Buenos Aires, Argentina

otropin(s), chorionic, pharmacodynamics- Gonadotro-pin(s), chorionic, therapeutic use

I n t r o d u c t i o n

SAL (Suction-Assisted Lipectomy) and ObesityFew surgical procedures aroused as much interestfrom plastic surgeons and the lay press as SAL did.Pioneered by the early reports of Fischer and Fi-scher [103] and Schrudde [273], SAL reached itsheyday after the publications of Illouz [159-162]and Kesselring [186-189]. Actually, SAL has be-come the "prima donna" in the surgical armamen-tarium of plastic surg eons, and nearly no part of thehuman anatomy is spared, including the thighs,knees, neck, buttocks, calves, arms, breasts, flaps,back, and abdomen. Patients under and over the ageof 50 have, the refore, experienc ed the back-and-forth movemen t of a cannula connected to a suctionpump [72-73b, 107, 128, 145-146, 186-189, 250,308a-b, 326]. Cautious words about SAL are scarce[69, 124,322] com par ed with the myri ad of enthusi-astic reports. The number of SAL performed sur-passes any other aesthetic surgical procedure andthis tendency is growing [4].

Nevertheless, because SAL is a novel surgicaltechnique, its precise indications remain the centerof dispute. Articles have been published that pro-pose a conservative approach to fat suction,whereas d iverse publications suggest SAL may be anuseful tool in the therapy of obesity [241]. The dif-ferences between the criteria are not of mere aca-demic interest. If SA L is the appropriate ma neuv er


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132 S A L a n d h C G M e t h o d f o r O b e si t y T re a t m e n t

2Fig. 1. Android (left) and gynoid ( r ight ) types of obesityFig. 2. The hypothetic long-term result from an overzealous SAL. Patient with a classical gynoid-type of obesity (left)showing waviness in thighs region and an android redistribution of fat after a SAL ( r i gh t ) . This "new" body fatdistribution forewarns a higher incidence of metabolic complications

for the managem ent of the obesity, then plastic sur-geons would receive the merit o f having developedan easy procedure that solves a disease that hasbeen present for thousands of years. But if SAL isn o t the adequate method for obesity therapy, thenpreoperative patient s e l e c t i o n becomes of utmostimportance.

B o d y F a t D i s tr i b u ti o n a n d S A LFat suction might have adverse effects in obese pa-tients: it is well known from Vague's report thatthere exist two types o f obesity, depending on bodyfat distribution: a gynoid type and an android type[312,314] (Fig. 1). The gynoid type of obesity tendsto accumula te fat in the hips, buttocks, thighs, andlower abdomen. In the android type, adipose tissuelargely localizes in the back, shoulders, and upperabdomen. Gynoid fatness is more resistant to diet-ing. The android type is easier to treat but shows anincreased incidence of clinical complications, suchas hyperlipemia, hypercolesterolemia , diabetes, hy-pertension, diabetes, and gout [313,316].Excessive fat removal by SAL may stimulate, inthe long run, counterregulatory balances resultingin adipocyte hypertrophy and/or hyperplasia fromthe adip ocytary pool. Fa ust and Kral concluded:" . . . rapid weight gain after a lipectomy cannotinvolve tissue that is no longer present, so it mayrequire hypert rophy of the remaining tiss ues. " [96].In the case of gynoid obesity, this compensatorygrowth after a lipectomy (or an overzealous SAL)

may occur in the upper part of the body. Thus, byforce of surgical treatment a "cosmetic" obesitymay evolve into a "medical" one [Fig. 2]. Thismodification of body fat distribution certainly doesnot benefit the patient. When compared with gynoidfatness, the android type of obesity shows an in-creased cardiovascular risk [313, 316].Alternatively, counterregulatory mechanismsmay generate adipocytary hypertrophy and/or hy-perplasia in the liposuctioned area. Figure 3 showsan obese patient twice liposuctioned elsewhere,showing recurrence both of obesity and body con-tour deformity.In our opinion, S AL has a definite place in bodycontour surgery provided that it is performed insmall quantities, in conspicuous fat accumulations,and for an aesthetic improvement of the body con-tour (Fig. 4) [325]. Therefore, today's plastic sur-geons should bear the responsibility for selectingthose patients who would benefit from a preopera-tive weight reduction program. During the pastseven years we have insisted that candidates for abody contour surgical procedure should correcttheir obese condition prior to the operation itself[319-325]. This is imperative, because o f the in-creased numbers of moderately obese patients com-ing to our consultation offices.In our exper ience , a most difficult issue is theselection of an adequat e obe sity therapy suitable toour plastic surgical requirements as well. Weightreduction programs offering an acceptable weightloss but poor skin tone are fairly common (Fig. 5).After many trials, we concluded that the hCG(human chorionic gonadotropin) program suited our


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T. Vogt and D. Belluscio 133

Fig. 3. Obese patient twice liposuc-t ioned elsewhere showing recurrenceof obesity and body contour deform-it y

A

Fig. 4 (A-C).servative SA L

J iIiIdeal anatomic sites to perform a con-

B

o

fne e ds a nd goa l s: r a p id w e igh t l o s s , e xc e l l e n t bodyc on to ur , a nd g ood sk in t one a f t e r t r e a tm e n t ( F ig . 6) .A s i s w e l l know n, t h i s s t r i k ing a ppr oa c h t o obe s i t yp r o vok e d se ve r a l ye a r s a go a g r ow ing w a ve o f cr i ti -cism [6, 14, 19, 28, 42, 60, 61, 74, 108,130, 140, 224,247, 256, 276, 294, 337] . Never the less , because ofr e c e n t da t a sugge s t i ng hCG migh t be l i po ly t i c invivo, w e be l i e ve t he w ho le sub j e c t de se r ve s a ne we v a l u a ti o n . F o r t h is o b j e c t i v e w e h a v e m a p p e d o u ta w o r k in g h y p o t h e s i s o n t h e s u b j e c t. C o n s e q u e n t l y ,the pu rpo ses of th is a r t ic le a re (1) br ie f ly revie wsome ne w t r e nds on o be s i t y c l a s s if i c a ti ons a nd sum-ma r i z e c u r r e n t c onc e p t s on obe s i t y a nd a d ipose t i s -

sue me ta b o l i sm a nd (2 ) d i s c us s s e ve r a l l i ne s o f e v i -de nc e t ha t sugge s t t ha t t he hCG me thod i s ac o m p l e t e p h a r m a c o l o g i c , d i e t e t i c , a n d b e h a v i o r a lm o d i f i ca t i on p r o g r a m f o r o b e s i t y t r e a t m e n t .

Part I: Overview of Obesity and Adipose Tissue" O b s e r v e t h a t t h e t h i ng s w h i c h a r e c o n s i d e r e d t o b er igh t t oda y a r e t hose w hic h w e r e c ons ide r e d t o beimposs ib l e ye s t e r da y . T he t h ings w hic h a r e t hough tw r ong t oda y a r e t hose w hic h w i l l be e s t e e me d r i gh tt o m o r r o w . " Hudhaifa


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134 SAL and hCG Method for Obesity Treatment

Fig. 5 (A,B ). Aesthetic result in a patient treated with a standardhypocaloric diet. Weight loss was 20 kg

Fig. 6. Patient before (A) and after(B) a full course of treatment (40days) under the hC G program. Weightloss was 16.3 kg

O B E S I T Y

Classification of ObesityCl in i c a l s i gns o the r t ha n w e igh t a nd he igh t a r e c u r -r e n t l y r e l e v a n t i n th e a s s e s s m e n t o f th e o b e s e p a -

t i en t . A c ons ide r a b l e bod y o f e v ide nc e sugge s t s t ha tf a t d i s tr i bu t i on p l a ys a p r ognos t i c r o l e i n the e va lua -t i on o f t h e d i s o r d e r o f o b e s i t y . A s m e n t i o n e d b e -f o r e , V a gue ' s r e por t w a s a ma jo r a dva nc e on t hesub j e c t . S imi l a r c onc lus ions r e ga r d ing t he c l i n i c a li m p o r t a n c e o f b o d y f a t t o p o g r a p h y w e r e p u t f o r-w a r d b y s e v e r a l a u t h o r s . K i s s e b a h ' s l a b o r a t o r y


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T . V o g t a n d D . B e l lu s c i o 1 3 5

Fig. 7. Abdominal (A) and gluteofemora, (B) types ofobesity. (Redrawn from [11])

social pressures to keep pounds off, statistics showsuccess in the opposite direc tion [1, 53, 191, 235].Interest in the disease and research on the topic arerelatively new. Until the early 1940s, the adiposetissue was a neglected subject [119], and obese pa-tients were generally blamed for gluttony, cheating,lack of will power, and greed [123, 127, 173, 184].Many students of obesity adhered to the nihilisticattitude that obesity is caused simply by overeating,and that it can be cured only by undereating. De-spite the patients' efforts, however, for many thedisease remained "incurable" [121].Fortunately, not everyone shared this gloomyopinion of the disease. A group of researchers feltobesity might be characterized by a basic disorderof energy metabolism. Direct and indirect data con-tributed to the researcher's conclusions.

classified the obesities in UBSO (upper body seg-mental obesity) and LBSO (lower body segmentalobesity) [92]: UBSO is character ized by a WHR(waist to hip ratio, the relationship between waistand hip circumference) close to or above I. LBSOshows a WHR below 1. A WHR close to or above 1forewarns of clinical complications such as athero-sclerosis, heart strokes, and infarcts. The Swedishschool categorized obesity in abdominal and glu-teofemoral types (Fig. 7) [31a-b, 201, 204]. Theformer is more prone to metabolic complications(diabetes, hypertension, heart strokes), but it is eas-ier to treat than the latter.The NHANES survey designed a classificationbased on the relationship between the BMI (bodymass index) and the sum of skinfold thickness(166a-b). Thus, individuals may be classified asobese-overweight, obese-lean, overweight notobese, and lean not obese. The incidence of hyper-tension and hypercholesterol emia was higher in theobese-not-overweight group.Recently, the National Institutes of Health pro-posed a major breakthrough on this subject. Thepanel concluded that a treatment for obesity wasadvisable even in discretely overweight patients,provided that a family history of obesity, obesity-related diseases, or personal antecedents of obe-sity-related diseases was present [235]. Conse-quently, obesity was declared a disease. Beingoverweight was not the single diagnostic tool usedto characterize the disorder [231,235].

" N o t b y F o o d A l o n e "The overall state of obesity treatment remains a dis-appointing subject [22, 34, 58, 83, 84, 121, 123, 129,163, 184, 212, 239, 292, 300]. Notwithstanding the

I n d i r e c t D a t aNeumann [232] conducted a study on himself. Dur-ing a prolonged control period he varied his dailyfood intake significantly. His weight, however, re-mained stable. He concluded that somehow hisbody managed to get rid of the surplus caloric in-take.Similar conclusions were advanced by Gulick[138] and Passmore [244]. The term " luxu scon -sumpt ion" was coined to describe these clinical ob-servations. The next step in the research was toinvestigate the mechanisms whereby the organismmaintained a relative constancy in body weight.Miller and Mumford [222] proposed that the extraingested calories were dissipated by heat loss dur-ing exercise, a conclusion not unanimously agreedto by other investigators [48]. Despite contradictoryevidence, it soon became apparent that there wasno direct relationship between daily food intake andbody weight.Sims published a classic report on this topic. Inhis study, normal healthy individuals fed with a highcaloric diet (up to 4000 kcal /day ) maintained a fairlystable weight during the test period. In those caseswhere weight was increased, normalization was at-tained by restoring subjects to a normal daily foodintake. Sims concluded: "A primary disturbance ofthe mechanisms which monitor energy balance ofthe body, and which regulate food intake, couldsecondarily lead to metabolic and endocrinechanges; these in turn could contribute to perpetu-ate obesit y [280, 281]." Interestingly, not all thevolunteers for the study showed the same responseto a hypercaloric diet.Edho lm [89], after a series o f clinical exper imentsmeasuring caloric intake and energy consumption insoldiers, concluded that there were no significant


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1 3 6 S A L a n d h C G M e t h o d f o r O b e s it y T r e a tm e n t

G L U C O S E - , P H O S P H A T E

D I H Y D R O X Y A C IO N E P H O S P H A T ENAD+H+ ~-

- r I " F A D H 2K - G L Y C E R O P H O S P H A T E

Fig. 8 . Possible "wa stefu l" or "fut i less cycles" in l ipidmetabolism. Let ter "A " points to the diversion of carbo-hydrates into the fat ty acid synthesis cycle; let ter "B " tothe hydro lysis-esteri f icat ion cycle. Both m etabol ic path-ways are less conservat ive from the bioenerget ic view-point

c o r r e l a t i o n s b e t w e e n b o d y w e i g h t a n d d a i l y f o o dc o n s u m p t i o n .

Direct DataD i r e c t e v i d e n c e f r o m s t u d ie s o f o b e s e p a ti e n t s w e r er ep o r t ed b y s ev e ra l au t h o r s . Mi l l e r [ 2 2 3 ] d emo n -s t r a t ed t h a t u n d e r w e l l - co n t ro l l ed co n d i t i o n s , a p e r -cen t ag e o f d i e ti n g o b e s e p a t i en t s f a i led t o lo s ew e i g h t w h e n c o m p a r e d w i t h t h e i r c o u n t e r p a r t s .S i n c e t h e s t u d y w a s p e r f o r m e d o n a n i n - p a ti e n t b a -s i s , t h e f a i l u r e s co u l d n o t b e a s c r i b ed t o a p o o r ad -h e r e n c e t o t h e d i e t . T h e r e a s o n s w h y t h e s e o b e s ei n d iv i d u a ls w e r e r e s i s t a n t t o c h a n g e r e m a i n e d u n e x -p l a i n ed .D i f f e r e n t r e p o r t s r e a c h e d t h e s a m e c o n c l u s i o n s :O b e s e s u b j e c t s d i d n o t a l w a y s o v e r e a t i n t h e e x -p e c t e d q u a n t i ti e s . S o m e o f t h e m w e r e , i n f a c t , e a t-i n g t h e s ame amo u n t o r l e s s t h an t h e i r l e an co u n t e r -parts [17, 44, 170, 171a-b, 246, 293].

Theories on Obesity GenesisS e v e r a l t h e o r i e s h a v e b e e n p r o p o s e d t o e x p l a in t h ep r o c e s s w h e r e b y o b e s e i n d i v i d u a l s m a i n t a i n a n a b -n o r m a l h i g h r e g u l at i o n o f b o d y w e i g h t. K e e s e y e ta l. s u g g e s t e d t h e c o n c e p t o f a " s e t p o i n t " f o r b o d yw e i g h t r eg u l a t i o n [1 7 9 -1 8 1 ] . Co n s i s t en t w i t h h i s r e -p o r t s , t h e o r g a n i s m r e g u l a t e s a s t a b l e b o d y w e i g h tb y m e a n s o f a p r e c i s e s y s t e m t u n e d t o a f ix e d " s e tp o i n t " . K e e s e y e t a l. p r o p o s e d t h a t o b e s e p a ti e n t sp o s s e s s a n a b n o r m a l l y e l e v a t e d s e t p o i n t. T h u s ,t h e i r o r g a n is m s a d j u s t e n e r g y m e t a b o l i s m t o a n i n-c r e a s e d l e v e l o f b o d y w e i g h t .

S o m e d a t a c o n t e n d t h a t o b e s e p a t i e n ts m a y s h o wa n a l t e r e d a c t i v i t y o f " f u t i l e s s " m e t a b o l i c c y c l e s[167 , 298]. Th i s im pl ies the co n t inual cycl in g o f sub-s t r a t e s t h ro u g h a s e r i e s o f s y n t h e t i c an d d eg rad a t i v er eac t i o n s w h i ch h av e t h e s ame i n i t i a l an d f i n a l en -e r g y s t a t u s . T h i s t y p e o f r e a c ti o n i s e n e r g y d e m a n d -i n g an d r e s u l t s i n l o s s o f th e e n e rg e t i c e f f i c i en cy o ft h e s y s t em , d i s s i p a t in g a g r ea t am o u n t o f h ea t . T h ef o l l o w i n g " f u t i l e s s c y c l e s " h a v e b e e n s u g g e s t e db ea r s o m e r e l ev a n ce i n o b es i t y (F i g . 8 ): (a ) t h e f a t t ya c i d s y n t h e s i s - o x i d a t i o n c y c l e a n d ( b ) th e t r ig l y ce r -i d e h y d r o l i s i s - r e e s te r i f i c a t io n c y c l e . B o t h c y c l e s in -v o l v e t h e H S L ( h o r m o n e - s e n s i t i v e l i p a se ) . T h i s isac t i v a t ed b y ad ren a l i n e , t h u s ex p l a i n i n g t h e i r l ip o -l y t i c an d p ro b ab l y t h e i r c a l o r i g en i c a f f ec t s o n ad i -p o s e t i s s u e [2 9 8 ] .T h e i s s u e o f w h e t h e r o b e s e p a t i e n ts s h o w a n in -c r e a s e d m e t a b o l i c e f f i c i e n c y , o r a t h e r m o g e n i c d e -fec t , s t i ll rem ains an op en q ues t ion [23 , 88 , 117 , 142,1 7 6 , 2 7 7 , 2 8 3 ] . Mo re r ecen t l y , i t h a s b een s u g g es t edt h a t o b e s e p a t ie n t s m a y s h o w a n i m p a i r m e n t o fFFA ( f r ee f a t t y ac i d ) mo b i l i za t i o n f ro m ad i p o s e t i s -sue [210].ConclusionsO b v i o u s l y m u c h w o r k r e m a i n s t o b e d o n e i n t hi sf a s c in a t in g f i e ld o f e n e r g y m e t a b o l i s m . H o w e v e r ,f r o m o u r p e r s p e c t i v e t h e f o l lo w i n g c o n c lu s i o n s m a yb e d r a w n :1. N o n o b e s e i n d i v id u a l s p r e s e r v e a s t a b le b o d yw e i g h t r eg a rd l e s s o f w i d e f l u c t u a t io n s i n d a i ly ca -lo r i c in take [66 , 70] .2 . S i m i la r r e g u l a t o r y m e c h a n i s m s s e e m t o o p e r -a t e i n o b e s e p a t ie n t s . U n f o r t u n a t e l y f o r th e m , t hi sr e g u l a t o r y s y s t e m m a i n t a i n s a n i n c r e a s e d l e v e l o fb o d y w e i g h t d e s p i t e p e r i o d s o f f o r c ed d i e t in g [2 06 ].W i t h r e s p e c t t o t h e p r o c e s s e s i n v o l v e d i n t h is b i o -e n e r g e t i c c y c l e , H i r s c h h a s e l e g a n t l y c o n c l u d e d :" T h e p e r s i s t e n c e o f o b e s i t y in th e f a c e o f w e l l- p u b -l i c ized i n fo rma t i o n o n t h e h ea l t h h aza rd o f o b es i t y. . . . s u g g e s ts t o m e th a t t h e r e i s a m o r e s u b tl ep r o b l e m o f o b e s i t y t h a t m a n y o f u s h a v e b e e n l e a dt o b e l i ev e" [1 5 1 ] .Obesity: A Multifactor DisorderE v i d en ce s u g g es t s t h a t o b es i t y i s a mu l t i f ac t o r d i s -o r d e r . A h u g e b o d y o f d a t a c o n c l u d e s t h a t g e n e t i c s[9, 39, 41, 52, 54, 125, 167, 297,304, 329], the envi-ronment [24, 43, 81, 82, 87, 156, 193, 245, 261,3 0 1 a ], p s y ch o l o g i ca l t r a it s [ 7 5, 1 2 2 , 2 5 2 , 2 5 8 ] , s o c i o -eco n o mi c l ev e l [ 5 , 1 2 , 2 5 9 , 3 0 1 a ] , d ev e l o p men t [9 0 ,1 72 , 18 2, 1 8 3 , 2 0 5 , 3 2 8 ] , an d a CN S ( cen t r a l n e rv o u ssys tem ) d i s tu r ba nce [7 , 21 , 49 , 116, 175 , 197 , 253]c o n t r i b u t e t o t h e g e n e s i s o r t h e m a i n t e n a n c e o f t h ed i s o r d e r . T h u s " n a t u r e " a n d " n u r t u r e " , i n v a r ia b l e


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T . V o g t a n d D . B e l l u s c ioT a b l e 1A. Site differences in subcutaneous fat metabolism after one week of therapeuticfasting of obese subjects (from [11])

137

Metabolic event Abdominal fat Femoral fatBasal metabolismCatecholamine action Profound changesNo change

Antilipolytic effect of No changeinsulinFat cell size Decrease

Less profound changesIncreased a-adrenergiceffectInhibition at post re-ceptor levelIncreased sensitivityNo change

T a b l e lB . Site differences in subcutaneous fat metabo-lism after one week of therapeutic fasting of obese sub-jects (from [11])Fat cell size F > A~Basal lipolysis rate F < ABasal lipoprotein lipase activity F > AInsulin action F > ACatecholamine action F < A

F - femoral fat cells; A = abdominal fat cells

proportions, are equally important in the consider-ation of obesity [17, 37, 51a, 56, 77, 135, 152, 168,339].

A d i p o s e T i s s u e

Lipoprotein Lipase (LPL)Lipoprotein lipase (LPL) is an enzyme that hydro-lyzes plasmatic VLD L (very-low-density lipopro-teins) and chylomic hrons, thus releasing FF A fromthe intravascular lumen. The adipocyte takes upthese FFA and reesterifies them to triglycerides(TG) in the interior of the fat cell (Fig. 9). Severalreports suggest that a high LP L adipose tissue ac-tivity, as seen in some obese subjects, predisposesthem to increased fat storage [131,238,257, 274].LP L acti vity was found to be higher in the femo-ral than in abdominal regions in women, except dur-ing lactation. During lactation, however, LP L activ-ity is decreased in women's femoral fat pads. Thesefindings suggest that femoral adipose tissue pos-sesses a particular metabolic specialization duringlactation [254].

Heterogeneity and Multiple Physiological Aspectsof the Adipose TissueThe adipose tissue is not a uniform mass randomlydistributed throughout the human body. Dependingon topographic localization, adipocytes possess dif-ferent sensitivities to hormones, enzymes, drugs,and fast ing periods [10, 11, 38, 91, 177, 203, 287,288, 306, 315]. The processes of lipolysis and lipo-genesis in adipocytes are subject to the action ofseveral ho rmones and drugs (for review see [78]). Ithas been observed that during fasting catechol-amines inhibit femoral fat lipolysis in women [10,11]. According to Arner [10, 11] these findings maybe explained by the recent observation that the/3-adrenergic receptor number is decreased in femoralfat pads during therapeutic fasting [I0, I1,240]. In-sulin binding to adipocytes is modified in differentfat deposits during therapeutic fasting (Tables laand lb) [91]. On the other hand, some evidenceconcludes that the adipose tissue is quite an activemass as far as the metabolism of FFA [78], steroidhormones [97a,b], and amino acids [310] is con-cerned.

Steroid HormonesThere exists an ext remely large pool of steroid hor-mones in adipose tissue, several times that ob-served in plasma [97a,b]. Conse quent ly, the adi-pose mass may be an important variable of steroidhormone metabolism in humans.

Adipocyte Regeneration in Adult Individuals?Earlier reports suggested that the adipose cell doesnot multiply in adults [29, 30, 47, 149, 268, 269].Based on this preliminary data, it was speculatedthat SAL could be the appropriate tool for the treat-ment of obesity [162]. Nevertheless, this enthusias-tic surgical approach to a longstanding problem ofhuman metabolism soon was over shadowed by aseries of reports that concluded that the adipocytemay, indeed, multiply in adult individuals. Evi-dence of this came from experiments in animals andthe long-term followup of obese patients.


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1 3 8 S A L a n d h C G M e t h o d f o r O b e s i t y T r e a t m e n t

Fig. 9. The mechanism of action ofLPL (lipoprotein lipase). The enzymehydrolyzes VLDL (very low densitylipoproteins) and Chyl. (chylomi-crons) from plasma, releasing FFA(free fatty acids) in the extracellularspace. The adipocyte (Ad.) uptakesthese FFA and reesterifies them backto TG (triglycerides). When needed,these TG are hydrolyzed back to FFAby the HSL (hormone-sensitive lip-ase) and released in the circulationcoupled to the albumin (Alb.) frac-tion.

Adipocyte Regeneration in RodentsRoth [264] demonstrate d that alter a l ipectomy, theremaining fat cells multiply in rats. Miller [226]showed evidence concerning a de novo productionof adipocytes in adult rats. Faust showed that undercertain conditions, specific rat adipose tissue padsmay regenerate [93, 96].

Adipocyte Regeneration in HumansFoley [105] concluded that overeating leads to re-cruitment of new adipose cells in moderately obesepatients. Sj6strom et al. suggested that the adiposecells multiply in adult subjects [282a,b]. One of hisreports was a long-term followup of obese women[282a]. Kral [199a,b], in a followup of three lipec-tomized women, observed that one had regainedthe weight she had before the operation, a secondpatient had to keep a rigorous diet to maintain herweight, and there is no data concerning the thirdpatient. Kral concludes: "Surgical reduction of fatmass does not seem to prevent a future weightgain." Taken together, these data suggest that thetotal adipose mass is under the control of some typeof regulatory mechanism. This " homeo stat ic" sys-tem might compensate for eventual losses of fattytissue through hypertr ophy and/or hyperplasia fromthe adipocytary pool.

Regulation of the Adipose Tissue MassMaintenance of a fairly stable weight throughoutlife or the recovery of the adipose mass after surgi-cal interventions strongly suggests that there existsa CNS (central nervous system) mechanism thatcontrols fat deposition and release in adipose tissue

(for review see [332]). The proposal of the hypotha-lamic region as the regulatory organ appears plausi-ble [209,332]. The hypothalamus has been reportedto play a regulatory role in the menstrual cycle [20,100], cardiac frequency [227], and immunity [76].Thus, it is reasonable to assume that body energyhomeostasis is modula ted in the hypotalamic regionas well [251,332] (Fig. 10). Howeve r, a major draw-back to this hypothesis lies in the difficulty to ex-trapolate some clinical conditions as observed inhumans (e.g., obesity) with the results of experi-ments in animals.

P a r t I I : T h e h C G M e t h o d f o r Ob e s i t y T r e a t m e n t"There are, it may be, so many kinds of voices inthe world, and none of them is without signifi-cance" I Corinthians

Introduct ionAs is well known, the first protocol for the manage-ment of obesity with hCG was reported in Lancet[278] by the late Dr. A.T.W. Simeons. However,previous publications concluded that hCG was auseful drug for the treatme nt o f certain clinical pre-sentations of adolescent obesity, except Fr6hlich'ssyndrome [65, 116].Since 1966 this clinic has managed obese patientswith the hCG m ethod. As experience was gained bytreating 12,000 obese subjects, modifications to theoriginal protocol were introduced. Uniform results,excellent body contour after treatment, and absenceof clinical complications are the main characteris-tics of this outstanding form of obesity therapy. The


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T . V o g t a n d D . B e l lu s c i o 1 3 9

f

entrlcular nucleus{ D o r s o m e d i a l u c l e u s

\

Preoptic~ _ . A n t e r i o r

Supraoptlc2~o m e d i a 1 n u c l e u

Optic chiasma.~--- ary bodyMedia cinereum

A n t e r i o r l o b e -hadeno ypophysis)

Pnt t. FS

andlbular stem \

i!o lo be %*r r (Neu roh ypo phys l )

4edulla Oblongata

Fig. 10. The hypothalamic region.Different hypothalamic nuclei andtheir relationships to pituitary glandcan be seen. PRL: prolactin; LH:luteinising hormone; FSH: folliclestimulating hormone; ACTH: adreno-corticotrophic hormone; TSH: thyroidstimulating hormone; GH: growthhormone. Hormones from the poste-rior part of pituitary: Vp: vasopre-sine; Oxy: oxitocyne

procedure was accep ted [80] until the mid-1970swhen, for several reasons, it fell from credibility:1. An excessive proliferation of the so-called"fa t clinics. " These institutions injected hCG undertotally uncontrolled conditions [19]. Unproper man-agement of the hCG protocol resulted in an in-creased rate of clinical complications [86].2. An overestimation of the real therapeutic pos-sibilities of hCG. Publicity lead the people to be-lieve that hCG was the "magic wand" that wouldcure their disease.3. A series of clinical tests, which nearly all [61,74, 108, 130, 140, 224, 276, 289, 294, 337] but onewell-controlled one [14] concluded that the methodwas of no use for obesity treatment.We have postulat ed elsewhere [320a-325] thathCG is not the magic solution to cure obesity. Adaily injection of hCG gives optimum results onlywhen used in a rational weight reduction program.Therefore, strict observation to the complete proto-col is mandatory.

A Hypothetical FrameworkThis clinic is engaged in a study program on thesubject. We have developed a working hypothesisbased on the results of our clinical experience, on

recent evidence from the field of obesity research,and on some speculative hypotheses. The latterwere introduced when experimental data were notavailable. The model is incomplete and much workremains to be done to test the validity of these hy-potheses.A Working Hypothesis in Obesity Therapy. Thebasic postulates of our model are (I) obesity is notthe same as being overweight, (2) obesity has physi-cal signs, (3) human obesity might be characterizedby a hypothalamic disorder, (4) the hCG methodcomprises pharmacologic, behavior modification,and dietetic aspects. The pharmacologic aspects are(a) hCG is lipolytic in vivo, (b) hCG may act at thehypothalamic level, (c) hCG affects mood behavior.1. Obesity is not the same as being overweight.As we have seen before, recent data indicates thatobesity is a different clinical entity than being over-weight. Several lines of evidence contribute to thishypothesis:Gynoid type of obesity is preserved from theclinical complications appearing in android obe-sity. When compared with similar weights, thelatter appears more "ma ligna nt" than the former[313, 316].Recent laboratory tests have reported abnor-

malities suggesting metabolic complications ofobesity in normal or near-normal weight subjects


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[26 7] . T h e re fo re , cu r r e n t c l a s s i f i ca t i o n s o f o b e -s i ty i n t e r m s o f b o d y w e i g h t m a y n o t c o r r e l a t ew i t h c l i n i ca l s ev e r i t y o f t h e d i s o rd e r .A c c o r d i n g t o t h e N H A N E S s u r v e y c o n c l u -s i o n s , i n c i d en c e o f h y p e r t en s i o n i s h i g h e r ino b es e b u t n o t o v e rw e i g h t i n d i v i d u a l s [ 1 6 6 a , b ] .T h e N a t i o n a l I n s t i tu t e s o f H e a l t h c o n s e n s u sp a n e l c o n c l u d e d t h a t a p p r o p r i a t e t i m i n g t o t r e a to b e s i t y m a y d e p e n d o n c l i n i c a l v a r i a b l e s o t h e rt h an h e i g h t an d w e i g h t [ 2 3 5 ] .T a k e n t o g e t h e r , t h e s e d a t a i n d i c a t e t h a t o b e s i t ya n d b e i n g o v e r w e i g h t a r e n o t i n t e r c h a n g e a b l et e r m s : t h e f o r m e r m a y b e a c l i n i c a l d i s e a s e ,w h e r e a s t h e l a t te r c o u l d b e a s i gn o f d i s e a s e , n o t ad i s ea s e i t s e l f [ 5 0 ] . Sh o u l d t h i s b e t r u e , t h en t h e a s -s e s s m e n t o f o b e s e s u b j e c t s s h o u l d i n c lu d e v a r i a b l e so t h e r t h an h e i g h t an d w e i g h t a l o n e .2 . Doe s obe s i t y hav e phy s i c a l s i gns? A s f a r a sw e k n o w , it w a s D r . A . T . W . S i m e o n s w h o d e -s c r i b ed fo r t h e f i r s t t i me p h y s i ca l s i g n s t h a t h e co n -s i d e r ed t y p i ca l o f o b e s i t y [2 79 ]: ( 1 ) o n e o r t w o fo l d so f s k in a r o u n d b o t h s i d es o f th e b a c k o r t h e c h e s t ,( 2) th e p r e s e n c e o f a f a t p a d o n t h e n a p e o f th e n e c ki n a n o t h e r w i s e m o d e r a t e l y o b e s e p a t ie n t , ( 3) a n o -t i ceab l e v a l g u m o f th e k n ees , ( 4) a f a t p ad i n s i d e t h ek n e e s . T h e s e p h y s i c a l s i g n s c o u l d b e " c l i n i c a lm a r k e r s " u s e d t o s e p a r a t e o b e s e in d i v id u a l s f r o mt h o s e w h o a r e s i m p l y o v e r w e i g h t . O b e s e p a t i e n t ss h o u l d b e t r e a t e d w i t h a m o r e e n e r g i c w e i g h t r e d u c -t i o n p r o g r a m b e c a u s e t h e y s h o w a h i g h e r i n c i d e n c eo f c l i n i ca l co mp l i ca t i o n s .

3 . Obe s i t y m i gh t be c harac t e r i ze d by a hy po t ha-lamic di sorder . N o t w i t h s t a n d i n g r e c e n t d a t a t h a ts u g g e s t th a t t h e a d i p o c y t e m i g ht b e t h e m a i n c a u s eo f o b es i t y [94 , 9 5 , 1 3 2, 2 6 2 ], t h e r e i s mu ch e v i d en cet h a t t h e t o t a l b o d y f a t mas s i s r eg u l a t ed b y a cen t r a ln e rv o u s s y s t em mo d u l a t o ry s y s t em [2 0 9 , 2 1 4 , 3 3 2 ] .T h e r e f o r e , d e s p i t e g e n e t i c i n f l u e n c e s m a y p r e d i s -p o s e ad i p o s e ce l l s t o accu mu l a t e l i p i d s [41 , 79 , 1 3 2 ,1 47 ], t h e o v e ra l l a c t i v i t y o f f a t d ep o s i t i o n an d r e -l e a s e m u s t d e p e n d o n a n i n t e g r a t o r y c i r c u i t , w h i c hs h o u l d c o n t r o l t h e m e t a b o l i c a c t i v it y o f d i v e r s e f a tce l l s a l l o v e r t h e o rg an i s m.A w e l l - s t u d i ed t o p i c i s t h e r e l a t i o n s h i p b e t w eenh y p o t h a l a m i c e x p e r i m e n t a l l e s io n s a n d th e d e v e l o p -m en t o f o b es i t y i n r a t s . I n 1 93 9 , H e t h e r i n g t o n a n dRa n s o n [14 3, 1 4 4 ] r ep o r t ed t h a t s ma l l e l ec t ro l y t i cl e s io n s i n t h e V M N ( v e n t ra l h y p o t h a l a m u s ) r e s u l te di n h y p e rp h ag i a an d o b es i t y . T h o u g h t h e f i r s t p u b l i -c a t i o n s f o c u s e d o n t h e m e t a b o l i c a n d e n d o c r i n e d i s-o r d e r s a c c o m p a n y i n g h y p o t h a l a m i c l e s i o n s , l a t e ro n s ev e ra l r ep o r t s i n s i s t ed t h a t a b a s i c mo d i f i ca t i o ni n e a t in g b e h a v i o r ( h y p e r p h a g i a ) h e r a l d e d t h e o n s e to f m e t ab o l i c ab n o rm a l i t i e s ( h y p e r i n s u l in emi a )[ 8 a ,b , 1 8 5 , 2 8 6 , 2 9 5 , 2 9 6 ] . H o w e v e r , r e c e n t i n v e st i-g a t i o n s s u g g es t t h is i n t e rp r e t a t i o n ma y b e in co r r ec t .A c u r r e n t f o r m u l a t i o n f o r t h e s e s y n d r o m e s p r o -p o s e s t h a t n e u r a l l y m e d i a t e d h y p e r i n s u l i n e m i a i s

t h e p r i m a r y f a c t o r c o n t r i b u t in g t o e x c e s s i v e f a t a c -cu m u l a t i o n [1 64 , 1 6 5] . T h i s co n cep t i s n o t s h a red b yal l inves t iga to rs [134 , 295 , 296] .D es p i t e t h e co n t ro v e r s y o n t h e s u b j ec t , i t i s g en -e r a l l y a g r e e d t h e h y p o t h a l a m u s s o m e h o w p l a y s ar e g u l a t o r y r o le i n th e m e c h a n i s m o f en e r g y m e t a b o -l is m r eg u l a t i o n [6 7, 11 2, 1 20 , 1 5 8 , 1 6 9 , 2 0 9 , 2 1 4 , 2 1 5 ,225 , 243 , 251 , 272 , 332] . Never the less , a majorp ro b l em l i e s in t h e ex t r ap o l a t i o n o f t h e r e s u l t s o b -t a i n ed i n an i ma l ex p e r i me n t t o t h e c l i n ica l co n d i t i o no f o b e s i t y a s o b s e r v e d i n h u m a n s . E x c e p t f o r ah an d fu l o f ca s e s [4 9 , 6 4] n o d em o n s t r a b l e h y p o -t h a l a m i c l e s i o n s h a v e b e e n r e p o r t e d i n c o m m o no b es i t i e s . T h u s , i t ap p ea r s t h a t ex p e r i me n t a l an i ma lm o d e l s o f o b e s i t y a r e o f l im i t e d v a l u e w h e n c o n s i d -e r i n g h u m a n o b e s i t y ( f o r a r e v i e w o n e x p e r i m e n t a la n d g e n e t i c m o d e l s o f an i m a l o b e s i t y s e e [ 5 1b ,101]).A r e a s o n a b l e a l t e r n a t i v e t o t h i s p r o b l e m m a y b et h a t h u m a n o b e s i t y m i g ht b e c h a r a c t e r i z e d b y a s u b -t l e h y p o t h a l ami c d i s o rd e r , s t i l l n o t acces s i b l e t ocu r r en t d i ag n o s t i c me t h o d s [1 1 2 , 2 7 2 ] . I n d i r ec t ev i -d en ce t h a t s u p p o r t s t h i s h y p o t h es i s i s s een i n s ev -e r a l ex p e r i en ces i n h u m an s . A m at ru d a e t a l . [7 ]d e m o n s t r a t e d t h a t a g r o u p o f o b e s e m a l es s h o w e da n a b n o r m a l r e s p o n s e t o 1 0 0 / z g o f G n R H ( g o n a d o -t ro p i n r e l ea s i n g h o rmo n e) . J u n g e t a l . [ 1 7 4 ] co n -c l u d e d t h a t w o m e n w i t h fa m i li a l o b e s i t y h a v e a h y -p o t h a l a m i c f u n c t i o n d i s o r d e r w h i c h w a s n o t t o t a ll yco r r ec t ed a f t e r w e i g h t l o s s . K o p e l man e t a l . [ 1 9 5 ,1 9 6 ] , a f t e r s t u d y i n g t h e p ro l ac t i n (PRL ) r e s p o n s e t oi n s u l i n - i n d u c e d h y p o g l y c e m i a , c o n c l u d e d t h a t h y -p o t h a l a m i c f u n c t i o n i s d is t u r b e d i n m a s s i v e o b e s i t y .T h e c a u s e s f o r t h i s r e g u l a t o r y d i s o r d e r a r e p r e s -e n t ly u n k n o w n .A H y p o t h a l a m i c O p i o id D i s o r d e r in H u m a nObesi ty?R e c e n t d a t a f r o m t h e o p i o id r e s e a r c h f i el d o p e n e d an e w p e r s p e c t i v e i n th e c o n s i d e r a t i o n o f h u m a n o b e -s i t y : O b es i t y mi g h t r e s u l t f r o m an o p i o i d r eg u l a t o ryd e ran g emen t i n t h e d i en cep h a l i c r eg i o n [2 2 0 ] . Sev -e r a l d a t a s u g g e s t t h a t C N S o p i o i d s r e g u l a t e e n e r g ym e t a b o l i s m [ 1 9 2 , 2 1 6 - 2 1 8 , 3 3 5 ] a n d i n ge s t io n o f n u -t r i en t s [126 , 178 , 207 , 228-230 , 270 , 285 ,335] . Oneo f th e b e s t s t u d i e d n e u r o p e p t i d e s i s f l -e n d o r p h in . I th a s b een s u g g es t ed t h a t t h i s o p i o i d ac t s u p o n t h emech an i s m t h a t e l i c i t s ea t i n g t h ro u g h a " fo o d - r e -w a r d i n g " s y s t e m . T h i s c y c l e m i g h t f u n c t io n a s f ol -l o w s : F o o d i n g e s t i o n m a y i n c r e a s e C N S o p i o i d l e v-e l s [ 2 1 6 ] . T h i s c r ea t e s a " s e l f -g r a t i f y i n g " s en s a t i o n[ 62 ]. T h e r e f o r e , o b e s e s u b j e c t s s h o u l d b e c o m p e l l e dt o e l ev a t e t h e i r f o o d i n t ak e t o ma i n t a i n an e l ev a t edC N S o p i o i d c o n c e n t r a t i o n [ 6 2 ] .F r o m t h i s p e r s p e c t i v e , g l u t t o n y o b s e r v e d i no b e s e p a t i e n t s c o u l d b e e x p l a i n e d o n a b io c h e m i c a lb a s i s : A d d i c t i o n t o f o o d w o u l d b e a r e c o g n i z a b l e


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T . V o g t a n d D . B e l l u s ci o 1 41

CNS opioid disorder. Following this line of reason-ing, food restriction in obese subjects would de-crease the content of CNS endorphins, creating a"withdrawal sy ndrom e" similar to that observed indrug addicts. This hypothesis finds partial supportin the Gambert et al. report [115] that concludesthat fasting decreases the content of hypothalamic/3-endorphin in rat s.We hypothesize that modification of the contentof hypothalamic opioids may be related to energymetabolism as follows:1. Hypothal amic neuropeptide hypersecretion inobese patients may create a dependence on foodbecause food intake would increase CNS opioidconcentration [and thus self-gratification]. In thiscase, obesity would be maintained by an elevatedenergy input. A persistent high food intake levelcould lead to metabolic changes which may in turnperpetuate obesity [280, 281].2. The hypothala mus might be part of the diffuseneuroendocrine system, as proposed by Margules[217,218]. He suggested that opioids are the neuro-modulators of this system. Any stressful situati on--a diet, for example--could disrupt the homeostasisof the system. In the case of a diet, the period ofdecreased energy input would be compensated byphysiological adjustments in energy metabolism.This counte rregulatory phenomenon could result inthe maintenance of the body weight " set-poi nt."Finally, some evidence seems to suggest that thediencephalic region plays a regulatory function inthe metabolism of fat deposition and release. Re-search on hypothalamic neuropeptides may shednew light on the interpretation of obesity. Subtlemodification of the diencephalic opioid concentra-tion may be the cause or an indication of an under-lying neuromodulatory disturbance. This would, inturn, initiate the metabolic changes that lead to obe-sity.

4 . M u l ti p le A s p e c t s o f th e h C G P r o t o c o lP h a r m a co l o g i c A s p ec t : h C G i s l i p o l y t i c i n v i vo . Ac-cording to Simeons [278], obesi ty was charac terizedby the presence of an "abnormal" adipose tissue.These fat pads were localized in specific body ar-eas. Simeons suggested that hCG showed an affinityfor these fat masses. As far as we know, there areno reports proposing that hCG mobilizes this "ab-normal" fat. However, some data demonstrate thathCG can mobilize lipids from adipose tissue.Fleigelman [104] concluded that the administra-tion of hCG in rats decreased the a ctivity of u-glyc-erophosphate dehydrogenase and glucose-6-phos-phate dehydrogenase from the liver and adiposetissue. This could mean a diminished lipogenic ac-tivity in both tissues under hCG (Fig. 11).

* 3 0 ' -

25 AGPD

20--

915- - /~

- / / /

l O - -

- / / / .

a b

G6PD

a b

Fig. 11. The activity of two enzymes from rat adiposetissue before (A) and after (B) hCG administration.AGPD: soluble c~-glycerophosphate dehydrogenase;G6PD: glucose-6-phosphate dehydrogenase. (All enzy-matic activities are expressed as micrograms formazan/p~g nitrogen) (Drawn from [104])

Yanagihara [334] reported that hCG accelerates"no t only mobilization of fat from fat deposits, butalso its utilization in peripheral tissues, hCG in-creased the metabolism of injected fat emulsions,suggesting not only the acceleration of not only oxi-dation of fat, but increased ketone production in theliver and its utilization in peripheral tissues." Ro-met [260] reported that hCG intensifies the metabo-lism of rat brown adipose tissue.Administration of hCG in humans appears to in-crease t he release o f free fatty acids that varies withthe age of the subjects. Melichar et al. [221] demon-strated that hCG causes a marked FFA release innewborn infants. In adults, a single injection of hCGstimulated the release of FFA by P > 0.05 whencompared with placebo-treated individuals. This li-polytic action of hCG appears to be mediated. Tell[309] reported that adipocytes do not possess recep-tors for hCG. Therefore, the lipolytic action of hCGis mediated through an organ or system, which mayrelease a lipid-mobilizing substance in response tohCG stimulation.Alternatively, chCG (crude, commercial hCG)may exert an in vi tro lipolytic activity: commercialpreparations of hCG c ontains/3-endorphin [139], anopioid peptide with a suggested in vi tro lipolyticactivity [255].


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h C G m i g h t a c t a t h y p o t h a l a m i c l e v e l . At th i sp o i n t , i t s e e m s r e l e v a n t t o d i s c u s s s o m e d a t a r e -g a r d in g h C G . h C G i s a g l y c o p r o t e i c h o r m o n e , n o r -m a l l y s e c r e t e d b y t r o p h o b l a s t i c c e ll s o f t h e p l a c e n t ad u r i n g p r eg n an cy [27 5 ]. I t co n s i s t s o f t w o d i s s imi -l a r , s e p a r a t e l y b u t c o o r d i n a t e d l y t r a n s l a t e d c h a i n sca l l ed t h e a l p h a an d b e t a s u b u n i t s [ 2 7 , 5 9 , 1 0 2 , 2 4 9 ,3 1 7 , 3 1 8 ] . T h e t h r ee p i t u i t a ry h o rmo n es L H ( l u -t en i z i n g h o rmo n e) , FSH ( fo l l i c l e s t i mu l a t i n g h o r -m o n e ) , a n d T S H ( t h y r o i d s t i m u l a t i n g h o r m o n e ) a r ec l o s e l y r e l a t ed t o h C G i n t h a t a l l f o u r a r e g l y co s y l a -t e d a n d h a v e a d i m e r i c s t r u c t u r e c o m p r i s i n g A l p h aa n d B e t a c h a in s a s w e l l . T h e a m i n o a c i d s e q u e n c e so f t h e a l p h a c h a i n o f a ll f o u r h u m a n g l y c o p r o t e i nh o rmo n es a r e n ea r l y i d en t i ca l , t h e ami n o ac i d s e -q u e n c e s o f th e b e t a s u b u n i t s d i f f e r b e c a u s e o f t h eu n i q u e i mmu n o l o g i ca l an d b i o l o g i ca l ac t i v i t i e s o fe a c h g l y c o p r o t e i c h o r m o n e [ 2 6 3 ]. /3 - h C G c o n t a i n s aca rb o x i l i c r e s i d u e o f 3 0 ami n o ac i d s t h a t a r e ch a rac -t e r i s t ic o f h CG [2 5 -2 7 ] .I t s n a m e , h u m a n c h o r i o n i c g o n a d o t r o p i n o r i g i -n a t e d w h e n i t w a s f o u n d t h a t h C G m a t u r e d t h e i n -f an t i le s ex g l an d s (g o n ad o t ro p i n ) an d t h a t i t w a ss ec re t ed b y t h e p l acen t a ( ch o r i o n i c ) [ 1 3 , 3 3 8 ] . Re -c e n t d a t a s u g g e s t , h o w e v e r , t h a t b o t h t e r m s c a n b eq u i t e mi s l ead i n g : n o rma l h u man t i s s u es [4 5 , 3 0 5 ,3 3 6 ] , p l a s ma f ro m n o n p reg n an t s u b j ec t s [ 4 0 , 2 4 2 ] ,t r o p h o b l a s t i c an d n o n t ro p h o b l a s t i c t u mo r s [5 5 , 6 8 ,7 1 , 1 5 3 , 2 3 6 , 2 6 5 , 2 6 6 , 2 9 1 , 3 1 7 ] , b a c t e r i a [3 , 1 6, 2 1 3,2 1 9 , 2 8 4 ], an d p l an t s [ 8 5 , 1 0 9 , 1 1 0 ] ex p re s s h C G o r ah CG - l i k e ma t e r i a l ( f o r r ev i e w s ee [1 57 ]) . Recen t l y ,i t h a s b een s u g g es t ed t h a t t h i s h CG - l i k e ma t e r i a lm a y a c t a s a l o c a l g r o w t h m o d u l a t o r y f a c t o r ( D .Be l l u s c i o , u n p u b l i s h ed ) .A s f a r a s th e s c o p e o f t h is a r t i c l e is co n ce rn e d , w es ee t h a t t h e h y p o t h a l ami c r eg i o n i s a t a rg e t o rg anf o r t h e e x t r a g o n a d a l a c t i o n s o f h C G . Y a g i n u m a[333] showed tha t in ra t s per iphera l ly in jec ted I25I-h C G c r o s s e s t h e b l o o d - b r a i n b a r r i e r a n d a c c u m u -l a t e s i n t h e h y p o t h a l ami c r eg i o n . H i ro n o [1 4 8 ] r e -p o r t e d t h a t h C G h a s a d i r e c t e f f e c t o n h y p o t h a l a m i cmed i an emi n en ce (ME ) , i n h i b i t i n g t h e s y n t h es i s an dr e l e a s e o f F S H a n d t h e r e l e a s e o f L H f r o m t h e a n te -r i o r p i t u i t a ry t h ro u g h t h e h y p o t h a l amu s . Bo a rd [3 6 ]d e m o n s t r a t e d t h a t h C G a d m i n i s t r a t i o n i n c r e a s e st h e s e c r e t i o n o f t h e g r o w t h h o r m o n e i n h u m a n s .h G H ( h u m a n g r o w t h h o r m o n e ) m a y p e r f o r m l i p o -l y t i c [ 98 ] an d ca l o r i g en i c [46 ] fu n c t i o n s i n h u man s .T h u s , h C G c o u l d s t i m u l a t e h G H s e c r e t i o n . T h i sw o u l d , i n t u rn , s t i mu l a t e l i p o l y s i s f r o m ad i p o s e t i s -s u e . A l t e r n a t i v e l y , a n d f r o m a p u r e l y s p e c u l a t i v ev i e w p o i n t , h C G c o u l d s t i m u l a t e , t h r o u g h t h e h y p o -t h a l amu s , t h e s e c r e t i o n o f a p i t u i t a ry l i p id -mo b i l iz -ing fac to r [57] .

h C G a n d m o o d b e h a v io r . A mos t in t r igu ing c l in i -c a l a s p e c t o f t h e h C G p r o g r a m i s t h e s e n s e o f w e l l-b e i n g o b s e rv ed i n t r ea t ed p a t i en t s [ 1 4 , 2 7 8 , 2 7 9 ,3 1 9 - 3 2 5 ] . H o w e v e r , t h e s e f i n d i n g s w e r e r e f u t e d b ys e v e r a l p u b l i c a t i o n s [ 13 0, 2 2 4 , 2 9 4 , 3 3 7 ] . N e v e r t h e -

l e s s , r ecen t d a t a may s h ed s o me l i g h t o n t h e s u b -j e c t : H a s h i m o t o a n d S a w a i r e p o r t e d t h a t c o m m e r -c i a l p r ep a ra t i o n s o f h CG co n t a i n / 3 - en d o rp h i n [ 1 39 ],a n e u r o p e p t i d e r e l a te d t o c h a n g e s i n m o o d b e h a v i o r[1 3 6 , 2 7 1 ] . Pu re h CG co n t a i n s / 3 - en d o rp h i n a s w e l l[ 2 ] . C o n s e q u e n t l y , w e h y p o t h e s i z e d t h a t t h e c o n -t e n t o f / 3 - e n d o r p h i n i n h C G m i g h t b e r e s p o n s i b l e f o rt h e s li gh t " e u p h o r i a " o b s e r v e d i n o u r p a t ie n t s . T h i so p i o i d mi g h t ac t i n t h e h y p o t h a l ami c r eg i o n , an a r eao f ma j o r s y n t h es i s o f / 3 - en d o rp h i n [11 3, 1 3 3, 1 36 ,1 9 8 , 2 7 1 ] . Bu t a ma j o r d r aw b ack t o t h i s s u p p o s i t i o nl ie s i n t h e f ac t t h a t ex c ep t f o r a f ew r ep o r t s [ 35 , 63 ,1 9 2 ] , s ev e ra l s t u d i e s co n c l u d e t h a t p e r i p h e ra l l y i n -j e c t e d / 3 - e n d o r p h i n d o e s n o t c r o s s th e b l o o d - b r a i nb a r r i e r , o r , i f i t d o e s , i t i s e it h e r t ak en u p b y t h eb r a i n o r b r o k e n d o w n w i t h e x t r e m e r a p i d i t y [ 1 3 7 ,154 , 200 , 208] . Only d i rec t admin i s t ra t ion to thec e n t r a l n e r v o u s s y s t e m s e e m s t o s h o w c l i n i c a l e f -fec t s [248] .I t o c c u r r e d t o u s , f r o m a p u r e h y p o t h e t i c v i e w -p o i n t, t h a t h C G m i g h t b e t h e " c a r r i e r " f o r / 3 - e n -d o rp h i n i n t o t h e b r a i n , d e l ay i n g i t s c a t ab o l i s m an dfac i l i t a t i n g i t s p en e t r a t i o n i n t o t h e b r a i n : h CGc r o s s e s t h e C N S b l o o d - b r a i n b a r r i e r [ 1 8 ] , a n d i ta c c u m u l a t e s i n t h e h y p o t h a l a m u s [ 33 3] . E x t r e m e l yl o w c o n c e n t r a t i o n s o f t h e c o m p l e x h C G / /3 - en -d o rp h i n a t t h e h y p o t h a l ami c l ev e l s h o u l d b e s u f f i -c i en t t o ex e r t a t h e r ap eu t i c e f f ec t : / ~ - en d o rp h i n i so n e o f th e m o s t p o t e n t o f t h e t e s t e d n e u r o p e p t i d e s[1 3 6 ] . A l t e rn a t i v e l y , / 3 - en d o rp h i n co u l d en t e r t h ebra in a t the sp inal cord l evel [118] .

T h e c o m p l e x h C G / / 3 - e n d o r p h i n m a y a c t i n o b e s ep a t i en t s a s f o l l o w s : ( 1 ) T h e h y p o t h a l ami c co n t en t o f/ 3 - en d o rp h i n d ec reas es d u r i n g s t a rv a t i o n [1 1 5 ] . I ft h e s a m e o b s e r v a t i o n w a s s e e n i n h u m a n s , t h e n e x -o g e n o u s / 3 - e n d o r p h i n m a y p r e v e n t t h e w i t h d r a w a ls y n d ro me t h a t acco mp an i e s a d i e t i n g p e r i o d . ( 2 ) I tc o u l d s t im u l a t e t h e s e c r e t i o n o f t h e h y p o t h a l a m i cG H R H ( g ro w t h h o r m o n e r e le a si n g h o rm o n e ) f a c t o rand hence l ipo lys i s [98] .S i n c e t h e a b o v e a r e s p e c u l a t i o n s , t h e y s h o u l d b er e a d w i t h c a u t i o n : m u c h w o r k r e m a i n s t o b e d o n et o t e s t t h e v a l i d i ty o f t h e s e h y p o t h e s e s .

B e h a v i o r M o d i f i c a t i o n A s p e c t . A f t e r S t u a r t ' s r e -p o r t [ 29 9] , d a t a o n t h e u t i li t y o f a b eh a v i o r m o d i f ica -t i o n p r o g r a m f o r o b e s i t y t r e a t m e n t b e c a m e a v a i l -able [99, 301b, 302, 303, 327, 330, 331]. The ideab e h i n d t h e s e p r o g r a m s i s t h a t th e p r i m a r y b e h a v i o rt o b e c h a n g e d i s e a t in g , a n d a n u m b e r o f e x e r c i s e sa r e d e s i g n e d t o s l o w t h e r a t e o f e a ti n g. F o r m e r b e -h a v i o r a l p r o g r a m s b a s e d o n o n l y b e h a v i o r m o d i f ic a -t i o n h ad l i t t l e s u cces s [1 0 6 , 3 3 0 ] . Recen t l y , h o w -e v e r , s a t i s f a c t o r y l o n g - t e r m r e s u l t s h a v e b e e nr e p o r t e d w i t h a c o m b i n a t i o n o f b e h a v i o r m o d if ic a -t i o n an d t h e ad m i n i s t r a t io n o f a v e r y l o w ca l o r ie d i e t[32 , 33 ,211] .

I n o u r o p i n io n , t h e p r o t o c o l h C G c o n t a i n s b e h a v -


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T . V o g t a n d D . B e l l u s c i o 1 4 3

T a b l e 2. A compar i son be tween the bas ic behavio r modi f i ca t ion t echniques comp r i sed inthe hCG pro tocol ( l e f t ) and those f rom a cur rent behavior modi f i ca t ion program ( r ight )(A) Dai ly vis i ts to the doctor(B) Dai ly weighing o f the pat ien t(C) Ext reme sens i tiv i ty of the metho d toda i ly d ie ta ry e r rors(D) Modificat ion of dai ly eat ing habi ts( E ) A p r o g r a m m e d m a i n t e n a n c e p e r i o d

( A , B ) R e i n f o r c e m e n t o f p r e s c r i b e d b e h a v i o r s(C) Se l f -moni tor ing of the pa t i en t s(D) Deve lopm ent of t echniques to cont ro l theac t o f ea t ing(E) Maintenance per iod a f t e r t rea tment

i o r m o d i f i c a t i o n p r o c e d u r e s t h a t a r e s i m i l a r t o t h eb a s i c g u i d e l in e s o f a s t a n d a r d b e h a v i o r m o d i f i c a t io n

p r o t o c o l ( T a b l e 2 ) .Dietetic Aspect. D i e t p l a y s a s p e c i f i c r o l e i n o b e -s i ty t h e r a p y : I t d e c r e a s e s e n e r g y i n p u t t h u s s t im u -

l a ti n g e n e r g y c o n s u m p t i o n f r o m f a t d e p o s it s . N os t u d y t h a t w e k n o w o f h a s r e p o r t e d c o m p l i c a t io n sw i t h t h e 5 0 0 - k c a l d i e t . R e c e n t l y i t h a s b e e n s h o w nc o n c l u s i v e l y t h a t t h e u s e o f th e v e r y - l o w - c a l o r i ed i e t f o r m a n a g i n g o f o b e s e p a t i e n t s i s s a f e [1 1 4, 1 55 ,190, 237 , 290] .

ResultsF i r s t w e w a n t t o a s k : D o e s a n e w c l a s s i f i c a t i o n o fo b e s i t y r e q u i r e a n e w c l i n i c a l t e s t ' ? I n o u r o p i n i o n ,t h e v a l u e o f a s t a n d a r d d o u b l e - b l i n d t e s t to e v a l u a t et h e h C G p r o g r a m s e e m s q u e s t i o n a b l e . T h e r e i s n od o u b t t h a t a 5 0 0 - k c a l d i e t w i l l r e n d e r a n a c c e p t a b l ew e i g h t l o s s i n p a t i e n t s w h o r e c e i v e a d a i l y i n j e c t i o no f h C G , a p l a c e b o , o r s i m p l y d i e ta r y a d v i c e [ 15 0 ,2 7 8 ]. O n t h e o t h e r h a n d , i f o b e s i t y a n d b e i n g o v e r -w e i g h t a r e m e d i c a l t e r m s t h a t d e f i n e d i f f e r e n t c l i n i -c a l c o n d i t i o n s , h C G s h o u l d b e t e s t e d a g a i n s t a p l a -c e b o o n l y in o b e s e p a t i e n t s [ 2 78 , 27 9 ]. S u c h ac l in i c al s t u d y h a s n e v e r b e e n d o n e b e f o r e a n d w o u l dr e q u i r e t h e c lo s e c o o p e r a t i o n b e t w e e n a r e s e a r c hl a b o r a t o r y a n d a d e p a r t m e n t o f i n t e rn i s ts . T h e l a t te rs h o u l d b e f u l l y a c q u a i n t e d w i t h t h e m i n i m a l d e t a i lso f th e h C G c o m p l e t e p r o t o c o l. T h e r e s e a r c h l abs h o u l d b e w i l li n g t o i n i ti a t e a r e s e a r c h p r o g r a m o nt h i s p o o r l y i n v e s t i g a t e d r e l a t i o n s h i p b e t w e e n h C Ga n d o b e s i t y .T h e f o l l o w i n g r e s u l t s a r e f r o m o u r c l i n ic a l e x p e r i -e n c e . W e p r e p a r e d a r a n d o m s e l e c t io n o f 4 5 0 p a -t i e n t s t r e a t e d w i t h t h e h C G m e t h o d b e t w e e n 1 9 7 1a n d 1 9 79 . R e s u l t s c a n b e s e e n i n T a b l e s 3 a a n d 3 b . I tb e c a m e c l e a r th a t w e i g h t lo s s u n d e r t h e h C G p r o t o -c o l i s m o s t s u b s t a n t i a l w h e n c o m p a r e d w i t h s t a n -d a r d w e i g h t r e d u c t i o n p r o g r a m s . F i g u r e s 1 2 - 1 7s h o w s o m e o f o u r o b t a i n e d r e s u lt s .

A t t h e t o t a l d o s e i n d i c a t e d f o r a c o m p l e t e c o u r s eo f t r e a t m e n t w i t h h C G ( 50 0 0 I U ) , n o c o m p l i c a t i o n sh a v e b e e n r e p o r t e d . G o n a d a l h y p e r s ti m u l a t io n s y n-

d r o m e [ 15 ] a n d a c u t e M e i g s s y n d r o m e [ 1 1 l ] a r e a l -w a y s r e l a t e d t o a h ig h e r d o s e o f h C G ( 2 0, 00 0 I U o rm o r e ) , g e n e r a l l y u s e d i n c o m b i n a t i o n w i t h h M G( h u m a n m e n o p a u s a l g o n a d o t r o p i n ) [ 2 3 3 , 3 0 7 ] . M i -n o r c o m p l i c a t i o n s h a v e b e e n r e p o r t e d : l o s s o f t e lo -g e n e f f l u v i u m h a i r [ 2 02 , 3 1 1] o b s e r v e d i n p a t i e n t ss u b j e c t e d t o a d i e t i n g p e r i o d a n d p a i n a t t h e i n j e c -t i o n si te o f a c o m m e r c i a l l y p r e p a r e d h C G , b u t n o tw i t h a d i f f e r e n t o n e [ 1 4 1 , 2 3 4 ] .

I n o u r e x p e r i e n c e t h e f o l l o w i n g m i n o r c o m p l i c a -t i o n s w e r e o b s e r v e d : ( 1) m e n s t r u a l c y c l e s d i st u r -b a n c e s i n 0 . 1 % o f p a t i e n t s. S e v e r a l o f o u r o b e s ep a t i e n t s w h o p r e s e n t e d a m e n o r r h e i c d is o r d e r s p r io rt o t r e a t m e n t r e v e r t e d t o n o r m a l c y c l e s w h e n w e i g h tw a s d e c r e a s e d ; ( 2) h a i r l o s s in l e ss t h a n 0 . 0 1 % o f t h et r e a t e d s u b j e c t s. T h e h a i r w a s o f t h e T e l o g e n e f f lu -v i u m ( m a t u r e h a i r ) t y p e . N o r m a l r e g r o w t h w a s o b -s e r v e d a f t e r t r e a t m e n t i n a ll c a se s . T h e r e w e r e n oc a s e s o f p e r m a n e n t a l o p e c i a r e p o r t e d i n w e l l o v e r1 2 , 0 0 0 t r e a t e d s u b j e c t .

C o n c l u s i o n sT h e a d v e n t o f S A L h a s d r a m a t i ca l ly i n c r ea s e d t h en u m b e r o f o b e s e p a t i en t s c o m i n g t o o u r c o n s u lt a -t i o n o ff i ce s . T h e r e f o r e , a c o o p e r a t i o n w i t h a p h y s i -c i a n w h o s p e c i a l iz e s i n o b e s i t y i s o f u t m o s t i m p o r -t a n c e . T h i s t e a m w o r k w i l l h e l p i n t h e p r o p e rs e l e c t i o n o f p a t ie n t s a n d t o d e c i d e w h e t h e r a m e d i -c al w e i g h t r e d u c t i o n p r o g r a m s h o u ld b e p e r f o r m e di n t h e f i r s t p l a c e .O b e s i t y i s a m u l t i f a c e t e d d i s o r d e r . P r e s e n t c l a s s i -f i ca t io n s i n c l u d e t h e a s s e s s m e n t o f h e ig h t , w e i g h t ,a d i p o s e t i s s u e d i s t r i b u t io n , a n d f a m i l ia l a n t e c e d e n t so f o b e s i t y o r o b e s i t y - r e l a t e d d i s e a s e s . C u r r e n t d e c i-s i o n s o n th e a p p r o p r i a t e t i m i n g o f o b e s i t y t r e a t m e n ta r e b a s e d o n a c a r e f u l a n a l y s i s o f t h e v a r i a b l e s l i s te de a r li e r . P a t i e n t s w h o a r e f i ve o r te n p o u n d s o v e r -w e i g h t s h o u l d b e t r e a t e d w i t h a w e i g h t r e d u c t i o np r o g r a m w h e n p e r s o n a l o r f a m i li a l a n t e c e d e n t s a d -v i se i t .

T h e a d i p o s e t i s s u e r e a c t s d i f f e r e n tl y t o h o r m o n e sa n d d r u g s , d e p e n d i n g i t s t o p o g r a p h i c a l l o c a l iz a t io n .C o n s p i c u o u s b o d y a r e a s s e e m t o b e m o r e r e s i s t a n tt o f a st i n g b e c a u s e o f t h e p a r t i c u l a r m e t a b o l i c c h a r -


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144 SAL and hCG Method for Obesity Treatment

Fig. 12. A 45-year-old patient before(A) and after (B) a weight loss of13.5 kg in a 35 day course with thehCG program. Note absence of skinsagging despite the significativeweight reduction

Fig. 13. Harmonious 12 kg weightloss in a 39-year-old patient treatedwith our protocol (40 days). Physicalsigns characteristic to obesity havedissappeared (A) before; (B) after

Fig . 14 . A 30-year-old male before(A) and after (B) a weight loss of17.3 kg, managed with the hCGmethod. It can be noticed the netimprovement of his abdominal type ofobesity


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T. Vogt and D. Bel luscio 145

Fig . 15 . Obe se 51- year - o ld pa t ien t be f or e ( A) and a f te r ( B) a we ight r educ t ion o f 16.2 kg in the cour se of a hC G t r ea tm ent(4 2 d a y s ) . O b s e r v e t h e d i s s a p p e a r a n c e o f s t r ia e c u t a n e a f r o m t h e l o w e r a b d o m e n

F ig . 16 . Obese pa t ien t be f or e ( A) andaf ter (B) a weight loss of 12.4 kg af tera c o u r s e o f 40 d a y s o f t r e a t m e n t w i t ho u r h C G p r o t o c o l . S y m m e t r i c b o d yf a t r educ t ion . Minimal s aggines s ofskin

F i g . 17 . T h i s p h o t o g r a p h s h o w s t h a t p r o p e r a e s t h e t i c r e su l t s c an b e o b t a i n e d w i t h t h e h C G m e t h o d w i t h o u t a n y s u r g ic a lpr ocedur e : a r m f r om an obese pa t ien t be f or e ( A) and a f te r ( B) the hCG t r ea tment


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acteristics of regional adipocytes. It seems thatsome cases of "resistant" obesity might be ex-plained by the decrease of the release of free fattyacid from adipose tissue, or a relative decrease inthe number of beta-receptors from adipose tissueduring therapeutic fasting. This relative decrease inbeta-receptor number may favor the alpha action(accumulation of lipids) of hormones.Individuals tend to maintain a fairly stable weightthroughout their life. For the obese, this "setpoint" of body weight regulation appears abnor-mally elevated. This hypothesis indirectly proposesthat there exist a mechani sm that controls fat depo-sition and release. Some evidence points to the hy-pothalamic region as the control organ.Counterregulatory mechanisms tend to compen-sate for the loss of fat mass. This compensatorygrowth may occur in body areas where adipocytehypertrophy and/or hyperplasia could result in in-creased morbidity. On the other hand, regrowth ofadipose tissue in lipectomized areas may result inthe recurrence of both obesity and body contourdeformity. Thus, surgical intervention on adiposetissue (SAL or lipectomies) is not advised as themethod of choice for obesity therapy. Neverthe-

T a b l e 3 A . Randomized study of 450 patients treated be-tween 1977 and 1979 in our clinic with the hCG protocolTotal patients: 450Females: 351Males: 99Age: females: 15-71 yearsmales: 16-75 yearsDegree of overweight (%)a: females: 54.23% (-+25.28)males: 74.03%(-+41.06)Average treatment (days): females: 41.24males: 41.68

a Degree of overweight is expressed according to the indi-cations of the table published by the Metropolitan LifeInsurance Company, 1959

less, SAL has a definite place in body contour sur-gery for the manageme nt of small, localized fat ac-cumulations.The hCG protocol is a safe, appropriate approachto obesity. It combines pharmacological, behaviormodification, and dietetic aspects. When properlymanaged, it results in a rapid weight loss and excel-lent body contour. Clinical complications and unfa-vorable results are related to hazardous modifica-tions o f the original protocol.There is some evidence that suggests that hCGpossesses lipolytic activity. Therefore, the basis ofuse of hCG for obesity treatm ent might be biochem-ical. Because hCG does not mobilize lipids in vitro,the hypothalamic region might be the intermediateorgan in hCG lipolytic action. On the other hand,hCG stimulates hGH secretion. Thus, it was hy-pothesized that hGH might be the lipolytic hormonesecreted to hCG stimulation.Commercial preparations of hCG contain/3-en-dorphin, and opioid peptide that may affect moodbehavior. We speculated that this neuropeptidemay be responsible for the sense of well-being ob-served in our hCG-treated patients.Since it has been reported that/3-endorphin doesnot cross the blood-brain barrier, it was suggestedthat hCG might act as a "carrier" for/3-endorphinin the brain. Alternatively, /3-endorphin may ac-count for an in vitro lipolytic activity.The hCG method comprises a behavior modifica-tion program that helps to a better handle obesepatients. There is some correlation between the be-havioral program included in the hCG protocol anda current behavior modification program for obesitytreatment.The 500-kcal diet as prescribed in the originalmethod proved to be safe and effective.Obesity is a widespread condition afflicting mil-lions of individuals all over the world. It is a slowkiller disease, causing disability, morbidity, anddiminution of the quality of life.

T a b l e 3 B . Randomized study of 450 patients treated between 1977 and 1979 in our clinicwith the hCG protocolBefore After Reduction

FemalesWeight (kg)Circumference (cm)Breast 105.23Waist 89.40Hip 111.64MalesWeight (kg)Circumference (cm)Waist 107.72Hip 108.97

81.60(-+14.25)

101.60(- 16.3)

70.61(-+10.04) 10.9998.10 7.1379.10 10.30101.54 10.1088.46(-+8.04) 13.1397.05 10.6798.57 10.40


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T. V og t and D . Be l lusc io 147The hCG method of treatment might be a reason-

able therapeutic alternative aimed at offering reliefto a longstanding unre solved p roblem of human me-tabolism.

R e f e r e n c e s1. Abraham S, Johnson CL: Prevalence of severe obe-sity in adults in the United States. Am J Clin Nutr33:364-369, 19802. Acevedo HF; Personal communication, October19853. Acevedo HF, Koide SS, Slifkin M, Maruo T,Campbell-Acevedo EA: Choriogonadotropin-likeantigen in a strain of Staphylococcusfaecal is and astrain of Staphylococcus s imulans: detection, iden-tification and characterization, Infect Immun 31(1):487-494, 19814. Adler J e t al: New bodies for sale. Newsweek Int

Mag May 27, 1985, pp 38-415. Akesode FA, Ajibode HA: Prevalence of obesityamong Nigerian school children, Soc Sci reed 17(2):107-111, 19836. Albrink M J: Chorionic gonadotropin and obesity'?Am J Clin Nutr 22(6):681-685, 19697. Amatruda JM, Hochstein M, Hsu TH, Lock woodDH: Hypothalamic and pituitary dysfunction inobese males, lnt J Obes 6(2):183-189, 19828a. Anand BK, Brobeck JR: Localization of a "feed-ing cen ter" in the hypothalamus of the rat. Proc SocExp Biol Med 77:323-324, 19518b. Anand BK, Brobeck JR: Hypothalamic control offood intake in rats and cats. Yale J Biol Med 24:123-140, 19519. Apfelbaum M, Fumeron F, Dunica S, Magnet M,Brigant L, Boulange A, Hors J: Genetic approachto family obesity. Study of HLA antigens in 10 fam-ilies and 86 unrelated obese subjects. Biomedicine33(4):98-100, 198010. Arner, P, Engfeldt P, Lithell H: Site differences inthe basal metabolism of subcutaneous fat in obesewomen. J Clin Endocrinol Metab 53:948-952, 198111. Arner P: Site differences in human subcutaneousadipose tissue metabolism in obesity. Aesth PlastSurg 8:13-17, 198412. Arteaga H, Dos Santos JE, Dutra de Oliveira JE:Obesity among school children of different socio-economic levels in a developing country. Int J Obes

6(3):291-297, 198213. Ascheim S, Zondek B: Die Schwangerschaftsdiag-nose aus dem Harn durch Nachweis der Hypophysevor dem Lappenhormon. Klin Wschr 7:1404-1411,192814. Asher WL, Harper HW: Effect of human chorionicgonadotropin on weight loss, hunger and feeling ofwell-being. Am J Clin Nutr 26:211-218, 197315. Aubert L: Development aigu d'un kyste de l'ovaireet grossesses quintuples chez une femme ayantregu successivement des gonadotropins seriques etchorioniques. Ann Endocrinoi (Paris) 21:176-182,1960.16. Backus BT, Affi-ont LF: Tumor-associated bacteriacapable of producing a human-chorionic gonadotro-pin-like substance. Infect Immun 32:1211-1215,1981

17. Baecke JA, Burema J, Frijters JE, Hautvas t JGAJ,Van der Wiel EF, Wetzels WA: Obesity in youngDutch adults. I: Socio-demographic variables andbody mass index. Int J Obes 7(l):1-12, 198318. Bagshawe KD, Orr AH, Rushwort AGJ: Relation-ships between concentration of hCG in plasma andcerebrospinal fluid. Nature 217:950-951, 196819. Ballin JC, White PL: Fal lacy and hazard: hCG, 500-Kcal diet and weight reduction. J Am Med Assoc230(5):693-694, 197420. Barnea ER, Naftolin F, Tolis G, de Cherney A:Hypothalamic amenorrhea syndromes. In: GivensE, Jr, ed, The Hypothalamus. Chicago: Year BookMedical Publishers, 1984, pp 147-17021. Bauer HG: Endocr ine and other clinical manifesta-tions of hypothalamic disease. J Clin EndocrinolMetab 14:13-31, 195422. Beck EC, Hubbard RS: A study of 63 patients be-fore and after weight reduction. NY State J Med 3 9 :1102-1107, 193923. Bessard T, Schutz Y, Jdquier E: Energy expendi-

ture and postprandial thermogenesis in obesewomen before and after weight loss. Am J Clin Nutr38:680-693, 198324. Bindon Jr, Baker PT: Modernization, migration andobesity among Samoan adults. Ann Hum Biol 12(1):67-76, 198525. Birken S, Canfield RE: Isolation and amino acidsequence of COOH-terminal fragments for the p-subunit of human-chorionic gonadotropin. J BiolChem 252:5386-5391, 197826. Birken S, Fetherston J, Canfield RE, Boime 1: Theamino acid sequence of the prepeptides containedin the ~ and/3-subunits of human choriogononado-tropin. J Biol Chem 256(4): 1816-1823, 198127. Birken S: Chemistry of human choriogonadolropin.Ann Endocrinol (Paris) 45:297-305, 198428. Birmingham L , Smith K: Human chorionic gonado-tropin is of no value in the management of obesity.Can Med Assoc J 128:1156-1157, 198329. BjOntorp, P, Sj6st rom L: Numb er and size of adi-pose tissue fat cells in relation to human metabolismis human obesi ty. Metabolism 207:703-713, 197130. Bj6ntorp P, Carlgren G, Isaakson B, KrotkiewskiM, Larsson B, Sj6strom L: Effect of an energy-reduced dietary regimen in relation to adipose tis-sue cellularity in obese women. Am J Clin Nutr 285:445-452, 197531a. Bj6ntorp P: Adipose tissue in obesity (WillendorfLecture). In: Hirsch J, Van Itallie TB, eds, RecentAdvances in Obesity Research (IV). London: JohnLibbey, 1985, pp 163-1703lb. Bj6ntorp P: Regional patterns of fat distribution.Ann Intern Med 103:994-995, 198532. Bj6rvell H, Rossner S: Long-term treatment of se-vere obesity. Four -year follow-up of results of com-bined behavioral modification program. Br Med J291:379-382, 198533. Bj6rvell H, Rossner S: The attrition rate can bereduced in long-term behavioral treatment of obe-sity. Abstr Vth Int Congr Obesity. Jerusalem, Sep-tember 14-19, t986, p 6134. Blondheim SH, Kaufman M, Stein M: Comparisonof fasting and 800-1000 Kcal diet in obesity. LancetI:250-252, 196535. Bloom F et al: Endorphins: developmental, endo-crinological and behavioral actions. In: McIntyre


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1 4 8 S A L a n d h C G M e t h o d f o r O b e s i ty T r e a tm e n t

G, Szelke M, eds, Mollecular Endocrinology. Lon-don: Elsevier North-Holland Medical Press, 1979,pp 39-6436. Board JA: Levels of plasma hGH during administra-tion of human menopausal gonadot ropin and humanchorionic gonadot ropin. Ob stet Gynecol 31(l): 1 1 6 -118, 196837. Bogg RA: Genetic component of obesity (letter).Lancet II(7996): 1205, 197638. Bolinder J, Engfeldt P, Ostman J, Arner P: Sitedifferences in insulin receptor binding and insulinaction in subcutaneous fat of obese females. J ClinEndocrinol Metab 57(3):455-461, 198339. Borjeson M: The aethiology of obesity in children.A study of 101 twin pairs. Acta Paediat Scand 65(3):279-287, 197640. Borkowski A, Marquardt C: Human chorionic go-nadotropin in the plasma of normal, nonpregnantsubjects. N Engl J Med 301:298-302, 197941. Bouchard C: Inheritance of fat distribution and adi-pose tissue metabolism. In: Vague J, Bj6ntorp P,

Guy-Grand B, RebuffE-Scrive M, Vague P, eds,Metabolic complications of human obesities, Ex-cerpta Medica (Congress Series 682). Amsterdam:Elsevier, 1985, pp 87-9642. Boyer A: L' hCG dans l'ob6sit6: non, non et non!Med Quebec Juin:81-82, 197643. Bradley PJ: Is obesity an advantageous adaptation?Int J Obes 6(1):43-52, 198244. Braitman L, Adlin V, Stanton JL: Obesity and ca-loric intake: Nationa l health and nutrition examina-tion survey of 1971-1975 (NHAN ES I), J Chron Dis38(9):727-732, 198545. Braunstein GC, Kamdar V, Rasor J, SwaminathanN, Wade ME: Widespread distribution of a chori-onic gonadotropin-like substance in normal humansubjects. J Clin Endocrinol Metab 49:917-925, 197946. Bray GA: Calorigenic effect of human growth hor-mone in obesi ty. Metabolism 29:119-122, 196947. Bray GA: Measurements of subcutaneous fat cellsfrom obese patients. Ann Intern Med 73:565-569,197048. Bray GA, Whipp B J, Koyal SN: The acute effectsof food intake on energy expenditure during cycle-ergometry. Am J Clin Nutr 27:254-259, 197449. Bray GA, Gallagher TF: Manifestations ofhypo tha-lamic obesity in man: a comprehensive investiga-tion of eight patients and a review of the literature.Medicine 54(4):301-330, 197550. Bray GA: To treat or not to trea t--t hat is the ques-tion? In: Bray GA, ed, Recent Advances in ObesityResearch (II). London: Newman Publishing Co.,1978, pp 248-26551a. Bray GA: Human obesity and some of its experi-mental counterpar ts. Ann N utr Alimen 33(1): l 7-25,19795lb. Bray GA, York DA: Hypothalamic and geneticobesity in experimental animals: an autonomic andendocrine hypothesis. Physiol Rev 59(3): 719-809,197952. Bray GA: The inheritance of corpulence. In: CioffiLS, James WPT, Van Itallie TB, eds, The BodyWeight Regulatory System. New York: RavenPress , 1981, pp 185-19553. Bray GA, McCall J: Dieting: The losing game. Time127(3):42-48, 1986

54. Breckenbridge WC, Little JA, Alaupovic P, Lind-gren FT, Kursis A: Abnormal triglyceride clearancesecondary to familial apolipoprotein C-II defi-ciency. In: Angel A, Hollenberg CH, RoncariDAK, eds, The Adipocyte and Obesity: Cellularand molecular mechanisms. New York: RavenPress , 1983, pp 137-14855. Broder LE, Weintraub BD, Rosen SW: Influence ofchemotherapeutic agents on chorionic gonadotro-pin c~-subunit secretion in a human lung cancer cellline (chAGo): Discordance of secretion and cyto-toxic effects. J Natl Cancer Inst 61(2):349-351,197856. Brownell KD: Behavioral, psychological, and envi-ronmental predictors of obesity and success atweight reduction. In t J Obes 8(5):543-550, 198457. Burns TW, Hales CN, Stockell Hartree A: Obser-vations on the lipolytic activity of human serum andpituitary fractions in vitro. J Endocrinol 39:213-225, 196758. Campbell CJ, Campbell IW, Innes JA, Munro JF,

Needle AL: Further follow-up experience after pro-longed therapeutic starvation. In: Burland W, ed,Obesity. London: Churchill-Livingstone, 1974, pp281-29259. Canfield RE, Morgan FJ, Kammerman S, Bell J J,Agosto GM: Studies o f human chorionic gonadotro-pin. Rec Prog Horm Res 27:121-164, 197160. Cargille CM: Human chorionic gonadotropin not in-dicated for obesity. J Am Med Assoc 219(11): 1485-1486, 197261. Carne S: The action of chorionic gonadotropin inthe obese. Lancet II:1282-1284, 196162. Carr KD, Simon E J: The role of opioids in feedingand reward elicited by lateral hypothalamic electri-cal stimulation. Life Sci 33:563-566, 198363. Catlin DH, Gorelick DA, Gerner RH, Hui KK, LiCH: Clinical studies with human/3-endorphin. In:Beers AF, Bassett EG, eds, Polypeptide Hor-mones. New York: Rave n Press, 1980, pp 337-35264. Celesia GG, Archer CR, Chung HD: Hyperphagiaand obesity, relationship to medial hypothalamic le-sions. J Am Med Assoc 246(2):151-153, 198165. Ceresa F: La terapie con ormone gonadotrope coroiale e con tiroide delle distrofie adiposo-ipersomicheipo-e normogenital dell'adolescente. CITer 4:24-40, 195366. Chinn S: In: Garrow S J, ed, Energy Balance andObesity. New York: North-Holland, 1974, pp 21-2367. Coimbra CC, Migliorini RH; Evidence for a longitu-dinal pathway in the rat hypothalamus that controlsfree fatty acids mobilization. Am J Physiol 245:E332-E357, 198368. Cole, LA, Birken S, Sutphen S, Hussa RO, PattilloR: Absence of the COOH-terminal peptide on ec-topic hCG-fl subunit. Endocrinology 110(6):2198-2200, 198269. Colon G: Liposuction: the downside (letter). PlastRecons tr Surg 75(1):132-133, 198570. Comstock GW, Stone RW: Changes in body weightand subcutaneous fatness related to smoking habits.Arch Environ Hlth 24:271-276, 197271. Couch WD: Combined effusion fluid turnout markerassay, carcinoembryonic antigen (CEA) and humanchorionic gonadotropin (hCG) in the detection ofmalignant tumours. Cancer 48:2475-2479, 1981


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T . V o g t a n d D . B e l l u s c io 1 4 9

72. Courtiss EH : Suction lipectomy: A retrospectiveanalysis of 100 patients. Plast Reconstr Surg 73(5):780-794, 198473a. Courtiss EH: Precise terminology for suction li-pectomy. Plast Reconstr Surg 75:(1):132, 198573b. Courtiss EH: Suction lipectomy: complicationsand results by survey (discussion). Plast ReconstrSurg 76(1):70-72, 198574. Craig LS, Ray RE, Waxler SH, Madigan H: Chori-onic gonadotropin in the treatment of obesewomen. Am J Clin Nutr 12:230-234, 196375. Crisp AH: Some psychiatric aspects of obesity. In:Bray GA, ed, Recent Advances in Obesity Re-search (II). London: Newman Publishing Co., 1978,pp 336-34476. Cross R J, Markesbery WR, Brooks WH, RoszmanTL: Hypothalamic-immune interactions. I. Theacute effect of anterior hypothalamic lesions on theimmune response. Brain Res 196:79-87, 197077. Daniels JS: The pathogenesis of obesity. PsychiatClin N Am 7(2):335-347, 1984

78. Davies JI, Souness JE: The mechanisms of hor-mone and drugs actions on fatty acid release fromadipose tissue. Rev Pure Appl Pharmacol Sci 2:1-112, 198179. Digy JP et al: HLA and familial obesi ty: evidencefor a genetic origin. In: Hirsch J, Van Itallie TB,eds, Recent Advances in Obesity Research (IV).London: John Libbey, 1985, pp 171-17580. Dietz RE, LaCroix E: Roundtable: Drug therapy inobesity, Part II. Ob Bar Med 9(1):15-25, 198081. Dietz W: Obesity in infants, children and adoles-cents in the United States. !. ldentilication.natural history and after effects. Nutr Rcs 1:117-137, 198182. Dietz WH Jr, Gor tmaker SL: Fac tors within thephysical environment associated with childhoodobesity. Am J Clin Nutr 39(4):619-624, 198483. Drenick E J: Weight reduction by prolonged fasting.In: Bray GA et al, eds, Obesity in perspective.Washington, DC: DEW Publ, 1975, pp 341-36084. Drenick E J, Johnson D: Weight reduction by fast-ing and semistarvat ion in morbid obesity: long-termfollow-up. Int J Obes 2:t23-132, 197885. Duffus CM, Duffus JH, Orr AH: Inhibition of gib-berellic acid biosynthesis by chorionic gonadotropinduring cereal grain germination. Experientia 26(12):1296-1297, 1970.86. Dunn CE: Human chorionic gonadotropin forweight reduction. Am J Obstet Gynecol 120:855,197487. Durant RH, Martin DS, Linder CW, Weston, W:The prevalence of obesity and thinness in childrenfrom a lower socioeconomic population receivingcomprehensive health care. Am J Clin Nutr 33(9):2002-2007, 198088. Dusmet H (quoted by Jequier E, Schutz Y): Does adefect in energy metabolism contribute to humanobesity? In: Hirsch J, Van Itallie TB, eds, RecentAdvances in Obesity Research (IV). London: JohnLibbey, 1985, pp 76-80Edholm OG: Energy expenditure and food intake.In: Energy balance in man. Apfelbaum M, ed,Paris: Masson et Cie, 1973, pp 51-60Edwards LE, Dickes WF, Alton IR, Hakanson EY:Pregnancy in the massively obese: course, outcome

89.

90.

and obesity prognosis of the infant. Am J ObstetGynecol 131(5):479-483,. 197891. Engfeldt P, Bolinder J, Ostman J, Arner P: Effectsof fasting on insulin receptor binding and insulinaction in different human subcutaneous fat depots.J Clin Endocrino l Metab 60(5):868-873, 198592. Evans D J, Kissebah AH, Vydelingum N, MurrayR, Hartz AJ, Kal khoff RK, Adams PW: Relation ofbody fat distribution to metabolic complications ofobesity. J Clin Endocrinol Metab 54:254-260, 198293. Faust IM, John son P, Hirsch J: Adipose tissue re-generation following lipectomy. Science 197:391-393, 197794. Faust IM, Miller WH: Hyperplast ic growth of adi-pose tissue in obesity. In: Angel A, Hollenberg CH,Roncari DAK, eds, The adipocyte and Obesity.Cellular and Molecular mechanisms. New York:Raven Press , 1983, pp 41-5195. Faust IM: Role of the fat cell in energy balancephysiology, In: Stunkard A J, Stellar E, eds, Eatingand its disorders. N ew York: Raven Press, 1984, pp97-10796. Faust IM, Kral J: Growth of adipose tissue follow-ing lipectomy. In: Cryer A, Van RLR, eds, NewPerspectives in Adipose Tissue. London: But-terworths, 1985, pp 319-33297a. Feher T, Bodrogi L: A comparative study of ste-roid concentra tion in human adipose tissue and theperipheral circulation. Clin Chim Acta 126:135-141,198297b. Feh~r T, Bodrogi L, Vallent K, Ribai Z: Role ofhuman adipose tissue in the production and metabo-lism of steroid hormones. Endokrinologie 80(2):173-180, 198298. Felig P, Martiss EL, Cahill JR: Metabolic responseto hGH during prolonged fasting. J Clin Invest 50:411-421, 197199. Ferguson JH: Learning to eat. Palo Alto, CA: BullPublishing Co., 1975100. Ferin M, Van Vugt T, Wardlan S: The hypotha-lamic control of the menstrual cycle and the role ofendogeneous peptides. Rec Prog Horm Res 40:441-485, 1984101. Festing MFW (Ed): Animal models of obesity. Lon-don: MacMillan, 1979102. Fiddes, JC, Talmadge K: Structure, expression andevolution of the genes for the human glycoproteichormones. Rec Prog Horm Res 40:43-78, 1984103. Fischer A, Fischer GM: Revised technique for cel-lulitis fat reduction in riding-breeches deformity.Bull Int Acad Cosmet Surg 2:40-42, 1977104. Fleigelman R, Fried GH: Metabolic effects of hu-man chorionic gonadotropin (bCG) in rats. Proc SocExp Biol Med 135:317-319, 1970105. Foley JE, Thuillez F, Bogardus C, Lilioja S, MottD: Short-term overfeeding increases adipose cellnumber in moderately obese subjects. In: Obesityand non-insulin dependent diabetes mellitus. JointConference of the American Diabetes Associationand the North American Association for the Studyof Obesity. October 3 0-Nov ember 1, 1985, Ab-stract 120106. Forey t JP, Goodrick S, Gotto AM: Limitations ofbehavioral treatment of obesity: review and analy-sis. Behav Med 4(2):159-174, 1981107. Fournier PF, Otteni FM: Lipodissection in body


20/26

1 50 S A L a n d h C G M e t h o d f o r O b e s it y T r e a tm e n t

sculpturing: The dry procedure. Plast ReconstrSurg 72(5):598-609, 1983108. Frank BW: The use of chorionic gonadotropin hor-mone in the treatment of obesity. Am J Clin Nutr14:133-136, 1964109. Friedman MH: Gonadotropic extracts from theleaves of young oak plants. P roc Soc Exp Biol Med37:645-646, 1938110. Friedman MH, Friedman GS: Gonadotropic ex-tracts from green leaves. Am J Physiol 125:486-490, 1939111. Friedrich F et al: Acute abdomen following hCGand hMG, Wien Klin Wschr 81:318-320, 1969112. Frohman LA: The syndrome of hypothalamic obe-sity. In: Bray GA, ed, Recent Advances in ObesityResearch (II), New York: Newman Publishing Co.,1978, pp 133-141113. Fuka ta J, Nakai Y, Takahashi K, Imura H: Subcel-lular localization of IR-/3-endorphin in rat hypothal-amus. Brain Res 195:489-493, 1980114. Van Gaal LF: Short and long-term effects of proteinsparing modified fast (PSMF) very low calorie diets.Abstr Vth Int Congr Obesity, Jerusalem, 14-19September, 1986, p 41115. Gambert SR, Garthwate TL, Pontzer CH, HagenTC: Fasting associated with decrease in hypotha-lamic/3-endorphin. Science 210:1271-1272, 1980116. Gamna C, Ceresa F: Le distrofie di origine dience-falo-ipofisaria. Proc 51 Congr Meal Int Ed. Rome:Pozzi, 1950, p 34117. Garrow JS: Thermogenes is and obesity in man. In:Bjrntrop P, Cairella M, Howard A, eds, RecentAdvances in Obesity Research (III). London: JohnLibbey , 1981, pp 208-213118. Gerner RH, Catlin DON: Peripherally administered/3-endorphin increases cerebrospinal fluid en-dorphin immunoreac tivity. J Clin Endocrinol Metab55:358-360, 1982119. Gideon Wells H: Adipose tissue: a neglected sub-ject. J Am Med Assoc 114(22):2177-2183, 2284-2289, 1940120. Givens JR (ed): The Hypothalamus. Chicago: YearBook Medical Publisher, 1984121. Glennon JA: Weight reduction: an enigma. Arch IntMed 118:1-2, 1966122. Gold DD Jr: Psychologic factors associated wit

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