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Randomised controlled trials may not always be absolutely needed EDITOR--We disagree with Mullner's editorial[1] as it took a very narrow perspective on a case in which attention should have been [...]

Although the claim has been made that there are early descriptions of what today we call endometriosis and adenomyosis in theses presented in Europe in the late 17^t^h and during the 18^t^h centuries, the first description of the condition initially named 'adenomyoma' is that provided in 1860 by the German pathologist Carl von Rokitansky, who found endometrial glands in the myometrium and designated this finding as 'cystosarcoma adenoids uterinum'. Over the following 50 years 'adenomyoma' (and endometriosis) were considered pathologies separate from the so-called 'haemorrhagic ovarian cysts', and it was not until 1921 that this condition was recognized to be of endometriotic origin. The first systematic description of what is today known as adenomyosis was the work of Thomas Stephen Cullen who, at the turn of the 19^t^h century, fully researched the 'mucosal invasion' already observed by a number of investigators in several parts of the lower abdominal cavity. Cullen clearly identified the epithelial tissue invasion as being made of 'uterine mucosa' and defined the mechanism through which the mucosa invades the underlying tissue. In 1925, 2 years before Sampson created the term 'endometriosis', Frankl created a name for the mucosal invasion of the myometrium and clearly described its anatomical picture; he called it 'adenomyosis uteri' and explained that 'I have chosen the name of adenomyosis, which does not suggest any inflammatory genesis as do terms like adenometritis, adenomyositis, adenomyometritis, still employed'. The current definition of adenomyosis was finally provided in 1972 by Bird who stated: 'Adenomyosis may be defined as the benign invasion of endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium'.

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The relatively short history of hormonal contraception has been marked by a series of 'pill scares', all of which--after creating panic among users--were proven to be unfounded in terms of public health impact. The latest pill scare, provoked by regulatory action in the United Kingdom and the Federal Republic of Germany in response to the publication of a series of articles indicating a doubling of risk of deep venous thrombosis in users of oral contraceptives containing third-generation progestins, seems finally settled: both the British and the German Drug Regulatory Authorities have now reverted their verdict. The damage unfortunately stays: hundreds of thousands of women have been compelled to abandon the pill of their choice, often deciding to drop contraception altogether, thereby exposing themselves to unwanted pregnancy and--in a number of cases--to pregnancy termination. This latest episode should be turned into something positive: we need to learn that, in the case of drugs in widespread use, before restrictive action is taken--and except for very rare and specific instances--the scientific community must carry out an exhaustive debate on the reality and importance of the observed effects. Although the public should, in each instance, be properly informed, it is only after this process has been completed that restrictive action should be taken. It is hoped that, after this last episode, all concerned have learned this simple principle and will accept being guided by it from now on.

Progestasert devices releasing 65 micrograms of [14C]progesterone daily were inserted in 10 women 3 months prior to elective hysterectomy. Following surgery, specimens were examined by light and electron microscopy and by autoradiography. In three uteri, removed during the early follicular phase, there was a clear contrast between the appearance of the superficial portion of the endometrium in the zone immediately adjacent to the device, when compared to areas away from the progestasert. This difference became more pronounced in four specimens obtained at mid-cycle and tended to diminish during the luteal phase: the number of glands was still lower than normal, but stromal decidual reaction was apparent throughout the functional layer of endometrium; in addition, in portions away from the device, glands showed the characteristics of a secretory phase. Progesterone and/or its metabolites were abundant in the superficial epithelium and in the portion of the glands adjacent to the surface; and also well distributed in the stroma and in the capillary walls. Historadiography however, clearly showed that progesterone barely penetrated the deeper portion of the endometrium. This picture does not substantially change during the entire cycle.

The history of endometriosis is reviewed in the light of today's clinical and pathological knowledge of this disease. Prior to Sampson's report in 1921, attention was focused on the enclosed type of endometriosis, sited deep in the pelvis and called adenomyosis externa. Sampson's first hypothesis, that rupture of an ovarian endometrioma caused superficial peritoneal endometriosis, was probably changed after this observation that the free, superficial peritoneal implants reacted like eutopic endometrium. These implants were recognized as implants from menstrual blood regurgitated into the pelvic cavity. Adenomyosis externa, ovarian endometrioma and peritoneal endometriosis then came to be regarded as the same disease. In the light of today's knowledge, it may be important to remember this progressive understanding in the nosology of what is now universally called pelvic endometriosis.

In order to study the temporal relations in the biogenesis of testosterone, decapsulated testes of adult mice were incubated with carbon-14-labelled sodium acetate and attempts were made to isolate the most likely intermediates.Considerable quantities of radiochemically homogeneous squalene, lanosterol, cholesterol, testosterone and androstenedione, but no pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone sulphate or dehydroepiandrosterone sulphate were isolated. The same pattern of incorporation was found when gradually increasing amounts of non-labelled pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate or testosterone were added to the system as "trapping agents" or when Leydig cell preparations rather than decapsulated testes were used.The presence of 10 mIU of HCG greatly enhanced the de novoformation of testosterone, androstenedione and 5α-dihydrotestosterone but did not change the pattern of acetate incorporation.Radioimmunoassays of the incubation medium with or without added HCG, and carried out at different periods of time indicated the presence of gradually increasing amounts of testosterone and androstenedione together with some 5α-dihydrotestosterone, whereas only trace amounts of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone and dehydroepiandrosterone were present.An analysis of the incubated testes revealed that the addition of HCG significantly enhanced the content of testosterone, androstenedione and 5α-dihydrotestosterone. Little or no increase was observed as far as pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone or dehydroepiandrosterone were concerned.It is concluded that decapsulated testes of mice synthesize de novotestosterone from sodium acetate under conditions in which the formation of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone sulphate and 17-hydroxypregnenolone sulphate cannot be demonstrated.

The group of diseases, recently named 'benign proliferative disorders of the female tract1', has remained neglected for many years. The diseases include the well-known ovarian cysts, uterine leiomyomas and endometriosis, as well as their sequelae (such as menstrual disorders, adhesions, pelvic pains). Such nosographical disorders are very common; in fact they are believed to affect, although not in a serious way, up to 50% of women, particularly those in their fifties2. The main reason for the paucity of interest on the part of physicians and researchers in this pathology is probably due to the common belief that the therapy of these disorders was exclusively surgical, and, consequently, there was litde expectation of further progress.

The relatively short history of hormonal contraception has been marked by a series of 'pill scares', all of which-after creating panic among users- were proven to be unfounded in terms of public health impact. The latest pill scare, provoked by regulatory action in the United Kingdom and the Federal Republic of Germany in response to the publication of a series of articles indicating a doubling of risk of deep venous thrombosis in users of oral contraceptives containing third-generation progestins, seems finally settled: both the British and the German Drug Regulatory Authorities have now reverted their verdict. The damage unfortunately stays: hundreds of thousands of women have been compelled to abandon the pill of their choice, often deciding to drop contraception altogether, thereby exposing themselves to unwanted pregnancy and-in a number of cases -to pregnancy termination. This latest episode should be turned into something positive: we need to learn that, in the case of drugs in widespread use, before restrictive action is taken-and except for very rare and specific instances-the scientific community must carry out an exhaustive debate on the reality and importance of the observed effects. Although the public should, in each instance, be properly informed, it is only after this process has been completed that restrictive action should be taken. It is hoped that, after this last episode, all concerned have learned this simple principle and will accept being guided by it from now on.

Two once-a-month injectable contraceptive formulations, HRP112 (depot-medroxyprogesterone acetate, 25mg and estradiol cypionate, 5mg.) and HRP102 (norethisterone enantate, 50 mg and estradiol valerate, 5 mg,) were compared in two groups of women witn regard to effectiveness, reported complaints and reasons for discontinuation. A total of 2328 women were recruited into a seventeen-centre, randomized clinical trial. Follow-up was for a period of one year and resulted in a total of 10,969 women-months of experience of HRP112 and 10,608 women-months of experience with HRP102.

In the western world in general and Europe in particular, family planning services have not contributed to a decrease in fertility rates to a sustainable level, because these levels were already low before such services were introduced.Therefore, the question 'What benefits can be derived from family planning services?', should be rephrased as 'What has changed in the lives of women?' and a distinction needs to be made between industrialized and developing countries.Benefits of family planning in the lives of women can be divided into four categories:(1) The acquired freedom to choose easily the number of children they wish to have;(2) Improvements in their health thanks to the availability of modern contraceptives;(3) The impact of contraception on the struggle to promote the condition of women;(4) More globally, the differences between the north and the south of the world in the impact of family planning on women's development.

Three midgestation placentas were perfused at laparotomy during fifteen minutes with tracer amounts of [1,2-3H] testosterone [35S] sulphate sodium salt, and metabolites present in the placentas, perfusates and maternal urine specimens were analyzed.Most of the radioactive material administered was present in the placentas and perfusates; approximately 2% of it was recovered from the urine. More than 99.5% of the radioactive material recovered from the placentas and the perfusates was in a water soluble (conjugated) form. No unconjugated testosterone was found in these sources.Radiochemically homogeneous [1,2-3H] testosterone [35S] sulphate was isolated from the placentas, perfusates and urine specimens collected during the first 24 hours of experiment. The isotopic ratio of the conjugate isolated from these sources was very similar to that of the perfused material. Seventy per cent of the double labelled radioactive material recovered from the Day 1 urine samples was radiochemically homogeneous testosterone sulphate.The relative amounts of testosterone sulphate present in the Day 2 and Day 3 urine specimens showed a gradual decrease. This decrease was associated with an increase in tritium to sulphur-35 ratio.From the pooled extracts of all urine specimens, small amounts of exclusively tritium labelled conjugated 5α-androsterone and 5β-androsterone were also isolated. No 17β-oestradiol 17-sulphate was detected in any of the sources studied.It is concluded that little, if any, testosterone sulphate is hydrolyzed by the midgestation human placenta, and that a considerable part of the testosterone sulphate secreted by the foetus is transferred across the placenta to the mother in an unchanged form. The major part of the transferred testosterone sulphate is excreted in the urine; a smaller part of it undergoes hydrolysis with a subsequent metabolism of the steroid moiety.

Previable foetuses were perfused with 3H-labelled testosterone (T) plus 14C-labelled androstenedione (A), or with 3H-labelled dehydroepiandrosterone plus 14C-labelled A. In addition, in two experiments half of the liver and one adrenal of foetuses perfused with 3H-labelled A were incubated with 14C-labelled A. From the various tissues several products of aromatisation and hydroxylation were isolated in a radiochemically homogeneous form.Oestrogens were present only in the extracts of livers and in the perfusates. From the livers oestrone, 17β-oestradiol, 15α-hydroxy-oestradiol and oestriol were isolated. Following reduction with KBH4of the fraction containing 16epi-oestriol together with ring D hydroxy-ketones, 15α-hydroxy-oestradiol, oestriol and 16epi-oestriol were isolated. These oestrogens, which were present exclusively as conjugated material, were only formed from A and T, but not from dehydroepiandrosterone. Conjugated oestrone, but no 17β-oestradiol was isolated from the perfusates. No oestrogens were detected in the extracts of the adrenals, not even following the perfusion and subsequent incubation with large amounts of A. Oestrogens were also absent from the combined extracts of all other foetal tissues.Unconjugated 11β-hydroxy-androstenedione was isolated from the adrenals as the principal metabolite of A both in the perfusion and incubation studies. It was also isolated from the perfusates. Conjugated 11β-hydroxy-testosterone was isolated from the adrenals as a major metabolite of T. No unconjugated 1 1β-hydroxy-testosterone was detected in any of the perfusion or incubation experiments. Little, if any adrenosterone was present in the adrenals. However, this compound was isolated from the extracts of the lungs and residual tissues. No qualitative sex difference was found in the formation of any of the compounds isolated.The formation of 15- and 16-oxygenated oestrogens by the liver was contrasted by the absence of 15α-hydroxy-androstenedione, 15α-hydroxy-testosterone, 16α-hydroxy-androstenedione, or 16α-hydroxy-testosterone from any of the tissues. Lack of 16α-hydroxylation of A was also demonstrated following the incubation of A with homogenates of adrenals and livers.It is concluded that:aromatisation in the foetal organism takes place only in the liver and exclusively from α,β-unsaturated 3-ketosteroids,part of the conjugated oestrogen formed by the foetal liver is released into the foeto-placental circulation, mainly, if not entirely, in a ketonic form,15α- and 16α-hydroxylation of A and T is preceded by aromatisation and takes place only in the liver,part of the A secreted by the placenta to the foetus is returned to the placenta in the form of 11β-hydroxy-androstenedione.

Four female and four male previable human foetuses (18th to 21st week of gestation) were perfused with a combination of 3H-labelled testosterone (T) and 14C-labelled androst-4-ene-3,17-dione (A) and the principal unconjugated products of dehydrogenation and reduction as well as testosterone sulphate were studied in the perfusates and various foetal tissues.14C-labelled T derived from the metabolism of perfused A, and 3H-labelled A, originating from the perfused T, were isolated from all sources studied; as much as 2.1% of the administered A was isolated in the form of T-14C and 3.6% of the administered T was isolated as A-3H. No statistically significant sex difference was found in the interconversion of T and A; however, the extent of interconversion in one female foetus differed highly significantly (P< 0.001) from that taking place in all other foetuses.The isotopic ratios of the re-isolated A and T indicated that the interconversion was complete in the liver, partial in the gastrointestinal tract and rather limited in all other tissues.No reduction products were detected in the adrenals. From the other tissues the following unconjugated 5β-reduction products were isolated: 5β-androstane-3,17-dione from the gastrointestinal tract, liver and perfusates, 3α-hydroxy-5β-androstan-17-one (gastrointestinal tract, liver, carcass and perfusates), 5β-androstane-3α,17β-diol (liver), 17β-hydroxy-5β-androstan-3-one (liver).The following unconjugated 5α-reduction products were isolated: 5α-androstane-3,17-dione (gastrointestinal tract, liver, lungs, carcass and perfusates), 3α-hydroxy-5α-androstan-17-one (gastrointestinal tract, liver, lungs, carcass and perfusates), 3β-hydroxy-5α-androstan-17-one (lungs, carcass and perfusates), and 17β-hydroxy-5α-androstan-3-one (lungs, carcass and perfusates).The 5β-forms were predominant in the liver, their quantity exceeding that of 5α-forms by at least a factor of 100, the 5α-forms dominated the pattern in all other tissues. A sex difference in the reductive metabolism of A and T could not be ascertained. Testosterone sulphate was a major metabolite in the gastrointestinal tract and adrenals, but was not detected in the liver.On the basis of the isotopic ratios of the isolated compounds a concept is presented describing the principal pathways of the reductive metabolism of A and T in various tissues of human foetuses at midpregnancy.

In vitrodiffusion of [14C] megestrol acetate (MA) was studied before and after the subcutaneous insertion of polydimethylsiloxane implants (PDS) in the human. A certain period of equilibration before diffusion becomes constant is required for newly prepared capsules as well as for those extracted from the subcutaneous tissue within six months of the insertion. On the other hand, in vitrodiffusion from capsules that have remained in the human for periods over one year, does not require any equilibration. Up to six months, the release in vitroof megestrol acetate was not significantly changed, whereas it was greatly decreased when capsules were re-incubated following sojourn in the subcutaneous tissue for 18 or 24 months.A continuous wall of newly formed fibrotic tissue, proliferated in a circular manner was found around the capsules in all the cases studied. This fibrillary tissue was then surrounded by a fibrous adipose layer containing granulomas and giant-cells of the foreign body type.

Ovarian function was assessed in 10 healthy young women, before and after the insertion of 3 or 4 polydimethylsiloxane capsules filled with 20 mg of megestrol acetate. Each capsule released in vitro, approximately 20 μg/24 h of the hormone.Daily determination of the urinary excretion of FSH, LH, fractionated oestrogens and pregnanediol were performed in all subjects during one control cycle, the first and the third cycle after the insertion of the capsules. Out of 10, 8 control cycles were ovulatory according to all the parameters investigated. This compares with 15 ovulatory cycles out of a total of 20, examined after the insertion of the capsules.During treatment no changes were observed in the FSH excretion pattern; the mid-cycle LH peak was present in all ovulatory cycles, although it was usually much less evident under the action of megestrol acetate. The excretion of oestradiol was significantly increased in all subjects (P< 0.05) during the first cycle following implantation. Oestrone and oestriol excretion was also generally higher in patients bearing PDS capsules; however, this difference was not statistically significant. Pregnanediol levels were not affected by the treatment in all cycles considered to be ovulatory on the basis of all the parameters.The menstrual bleeding pattern did not change in the majority of cases. One patient had, during treatment with 3 capsules, two profuse break-through bleedings whereas another one became amenorrhoic two months after the insertion of 4 implants.It is concluded that megestrol acetate sustained release preparations do not inhibit ovulation under the experimental conditions used.

Tritium labelled testosterone and carbon-14 labelled testosterone sulphate were administered into the intact foeto-placental circulation in two subjects at laparotomy and the principal conjugated metabolites present in the placenta and various foetal tissues, as well as unconjugated testosterone were isolated and identified. More than 99% of the carbon-14 labelled material recovered from the various sources was in a water-soluble (conjugated) form, whereas water-soluble metabolites accounted for some 42% of the tritium labelled material.More than 70% of the carbon-14 labelled material isolated from all tissues studied, except the liver, was present in the form of testosterone sulphate; in the liver it amounted only to some 30%.Exclusively tritium labelled unconjugated testosterone was isolated in a radiochemically homogeneous form from the placental and liver extracts, and from the combined extract of all other foetal tissues. In addition, three exclusively tritium labelled conjugated metabolites were isolated: 5α-androsterone sulphate (placenta, lungs and carcass), 5β-androsterone sulphate (placenta, liver, gastro-intestinal tract, lungs and carcass) and 3β,5β-androsterone sulphate (liver). In addition to double labelled testosterone sulphate, which was isolated from every tissue studied, double labelled 5β-dihydrotestosterone sulphate was isolated from the liver. Moreover, 5β-androstane-3α,17β-diol was isolated from the liver following solvolysis of the monosulphate fraction and 11β-hydroxytestosterone sulphate from the adrenals following solvolysis and conversion of the product to 11β-hydroxyandrostenedione.The testosterone sulphate isolated from the adrenals exhibited the highest, and that isolated from the placenta, lungs and liver the lowest tritium to carbon-14 ratio.It is concluded that significant quantities of testosterone are converted to testosterone sulphate by the foetal adrenals and that neither the foetus nor the placenta is capable of hydrolysing testosterone sulphate. The foetal metabolism of testosterone sulphate seems to be characterized by the formation of 5β-oriented conjugated reduction products in the liver and by the formation of 11β-hydroxytestosterone sulphate in the adrenals.

3H-labelled androst-4-ene-3,17-dione and 14C-labelled testosterone were administered at laparotomy into the intact foeto-placental circulation and the principal metabolites present in the placenta and various foetal tissues were isolated and identified. Five subjects were investigated; all foetuses were females.Except in the liver, where there was a complete interconversion, in all tissues more testosterone was converted into androstenedione than vice versa.The following unconjugated (ether soluble) metabolites were isolated: 5β-androstane-3,17-dione from the liver, gastro-intestinal tract and residual foetal tissues; 3α-hydroxy-5β-androstan-17-one (liver, lungs, gastrointestinal tract, residual foetal tissues); 5β-androstane-3α,17β-diol (liver); 5α-androstane-3,17-dione (lungs, gastro-intestinal tract, residual foetal tissues); 3α-hydroxy-5α-androstan-17-one (lungs, gastro-intestinal tract, residual foetal tissues); 11β-hydroxyandrost-4-ene-3,17-dione (adrenals); oestrone (placenta and combined foetal tissues); 17β-oestradiol (placenta); oestriol (placenta).The following metabolites were isolated from the conjugated (water soluble) fraction of the liver: testosterone, 3α-hydroxy-5β-androstan-17-one, 3β-hydroxy-5β-androstan-17-one, 5β-androstane-3α,17β-diol, oestrone, 17β-oestradiol, oestriol. In addition, oestrone was isolated from the aqueous phase of the placentas, oestrone, 17β-oestradiol and oestriol from the aqueous phase of the combined foetal tissues, and 15α-hydroxy-oestradiol was detected and characterized in the extracts of placentas and livers.A high degree of enzymic stereospecificity in the reduction of the administered androstenedione and testosterone was observed in the various foetal tissues: 3α,5β-forms were predominant in the liver, with little, if any 3α,5α-forms present. In the lungs and residual foetal tissues, 3α,5α-products were predominant, whereas in the extracts of the gastrointestinal tract both types of reduction products were present in approximately equal amounts.

A newborn anencephalic monster was injected with carbon-14 labelled dehydroepiandrosterone and tritium labelled androstenedione and metabolites recovered from various tissues and blood specimens were analysed. Dehydroepiandrosterone was readily converted to dehydroepiandrosterone sulphate in all tissues studied. Furthermore, unconjugated as well as conjugated 5-androstene-3β,17β-diol and conjugated 16α-hydroxy-dehydroepiandrosterone were isolated from the liver. Very little, if any, of the injected dehydroepiandrosterone was converted to Δ4-3-ketosteroids, ring A reduction products or oestrogens.On the other hand, androstenedione was rapidly metabolized to testosterone, a variety of unconjugated and conjugated reduction products and conjugated oestrogens.From the different tissues, the following unconjugated compounds were isolated in a radiochemically homogenous form: testosterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), 5β-androstanedione (liver), 5β-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), epi-5β-androsterone (liver), 5β-androstane-3α,17β-diol and 5α-androstanedione (blood, combined extract of all organs), 5α-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), 5α-dihydrotestosterone (combined foetal organs except the liver) and epi-5α-androsterone (blood and combined foetal organs except the liver). From the solvolysed conjugatedfraction, the following steroids were isolated: 5β-androstane-3α,17β-diol (liver), 5β-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), epi-5β-androsterone (liver), 5α-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), testosterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus). The 5β-forms were predominant in the liver, whereas the 5α-forms dominated the pattern in all other tissues studied, including the blood.The data indicate that the androgen metabolism of the anencephalic monster studied, did not differ qualitatively from that of midterm foetuses.

Determination of radioactivity in urine and faeces was used to monitor absorption of labelled 6-methyl-17α-acetoxypregna-4,6-diene-3,20-dione from polydimethylsiloxane implants. Based on previously determined in vitrodiffusion rates, mean absorption was 60% in hamsters, 80% in rabbits, and 85% in rats during the first month after implantation. Thereafter, excretion of radioactive material has slowly decreased. After six months, the rate declined to 40% of the original value.

One female and one male foetus were perfused at midpregnancy with 17β-oestradiol-16-14C,17α-3H and metabolites were isolated in a radiochemically homogeneous form from the perfusates and various foetal tissues. The 3H/14C ratio of the perfused material was 60.2. Unconjugated and conjugated 17β-oestradiol and oestrone were isolated from all tissues studied. The 3H/14C ratio of the oestradiol isolated from all tissues, except the liver, agreed with the perfused one. The oestrone isolated from different sources did not contain any 3H-label.Unconjugated oestriol and conjugated oestriol, 16-epi-oestriol, 16α-hydroxy-oestrone, 16-oxo-oestradiol and 15α-hydroxy-oestradiol were isolated from the extracts of the livers. No 3H-label was present in 16α-hydroxy-oestrone, and only traces, if any, in 16-oxo-oestradiol. On the other hand, the isotopic ratios of 16-epi-oestriol, oestriol and 15α-hydroxy-oestradiol were between 1.5 and 5.0.It is concluded that a small but significant part of the oestriol, 16-epi-oestriol and 15α-hydroxy-oestradiol synthesized by the foetal liver is formed viaa direct hydroxylation of oestradiol.

One and five day old male and female rats were pinealectomized and their reproductive function studied when they matured. In females the fertility index was similar to untreated or sham operated groups. However, the females matured 8 to 9 days earlier as evidenced by the opening of the vaginal membrane. In males pinealectomy had no influence on testes development and accessory sex tissue weights. It is concluded that the regulatory function of the pineal gland with respect to gonadal function is a minor one.

Without Abstract: