contraception: prospects for the new millennium
Hair, F.C.W. Wu
of Medicine, University of Manchester, Manchester M13 9WL, UK
Asian J Androl 2000 Mar; 2: 3-12
AbstractEffective regulation of human fertility has global consequences in terms of resource depletion, pollution and poverty. Current family planning services predominantly target a female clientele with few significant developments in male fertility regulation for over a century. The last two decades have witnessed a gathering interest, initially from the scientific community, and laterally from industry, in the development of safe, reliable, reversible methods of contraception for men. This review summarises the methods of male fertility regulation which are currently available and critically examines the published data on novel developments in male hormonal contraception which offer the potential of improved contraceptive choice for all in new millennium.
1 IntroductionFamily planning services at present cater for a predominantly female clientele. The advent of the oral contraceptive pill in the late 1950s sparked a proliferation of many new female contraceptive methods and devices upon which family planning services, usually an offshoot of gynaecological practice, have become established to serve the needs of fertile women. However, men have traditionally or historically been the more important partner in contraception. Thus, until the second half of the 20th century, periodic abstinence, coitus interruptus, condoms and vasectomy, all of which are male-directed or male-oriented methods, were the only means for couples to limit family size. Indeed, the demographic transition from high to low fertility in Europe and North America in the 19th century was largely brought about through these methods, especially coitus interruptus. Recent estimates indicate that some 45 million men have had a vasectomy and 45 million men use condoms, which together with the substantial number still relying on withdrawal (Table 1), constitute at least one-third of total contraceptive usage in the world today. It is clear that men are active and willing participants in the practice of contraception, whose needs and demands are not met by current methods. This review summarises recent efforts to develop effective, safe and reversible contraceptive methods for men in the 21st century.
1. Current contraceptive prevalence in couples of reproductive age and
the typical first year failure rates of the individual methods.
from United Nations Populations Division 1994 & Hatcher et al
2 Current Methods
interruptus and periodic abstinence are associated with unacceptably high failure
rates and their popularity is on the decline in modern contraceptive practice
(Table 1). The only two current reliable methods available to men (condoms
and vasectomy) are based on historical practices developed from the 16th
and 19th centuries respectively.
detailed discussion on this surgical method of male sterilisation is outside
the scope of this review. However, since the 1960s, vasectomy has played
an increasingly important role as the principal method for male contraception
in men who have completed their family. Some 45 million men are estimated
to have undergone vasectomy. The single most important advantage of the
method is the very high efficacy (1-2 failures per 1000 procedures). Complications
include haematoma or infection in 5%, recanalisation in up to 3% and sperm
granulomata varying from 3-75%, with no reported mortality. Vasectomy
has at various times been linked to increased
disease risks (atherosclerosis, diabetes, immunological disorders) but has
generally been shown to be a reassuringly safe. Retrospective
surveys have suggested a modest increased predisposition to prostatic
and testicular tumours in vasectomised men in the USA. However, the reported
relationships were weak and
have not been universally observed. On the basis of current data, no changes
in vasectomy practice are warranted although ongoing prospective studies
should further clarify this situation.
of vasectomy reversal are highly variable depending on the time interval since
the original procedure, the skill and experience of the operator and the
type of procedure. In general, much more favourable results are obtained
with microsurgical techniques within 2 years after vasectomy. Potential
patients should expect to
achieve patency rates of 80% and pregnancy rates of 60% if reversal is
within 5 years after vasectomy. Two main factors limit the wider acceptability of
surgical vasectomy: the need for skin incisions and the uncertainty of
reversibility. New techniques such as no-scalpel vasectomy and percutaneous
transluminal vas occlusion have been or are being developed to make the
procedure simpler, less invasive as well as more predictably reversible.
3 Experimental approaches
poor basic understanding of the complex intratesticular regulatory mechanisms
underlying normal spermatogenesis makes it difficult to identify specific
testicular targets for pharmacological disruption.
Since both T and FSH are required for normal spermatogenesis, currently
the most realistic way to suppress spermatogenesis is via the endocrine
suppression of pituitary gonadotrophic drive to the testis thereby abrogating
Leydig cell steroidogenesis and nullifying FSH simultaneously (See
Figure 1). The consequent depletion of intratesticular testosterone
and loss of FSH action will result in a collapse of spermatogenesis characterised
by a block in spermatogonial maturation and disruption of premeiotic stages
of spermatogenesis without affecting stem cells[9,10]. Maintenance
stem cell population ensures that hormonal suppression of spermatogenesis
is invariably reversible. However, the need to induce total inhibition
of T production from the testis invariably creates a systemic
hypoandrogenic state. This dictates the need for exogenous T replacement
to maintain extratesticular secondary sexual functions such as sex drive,
potency and androgen-dependent metabolic functions on bone, muscle and
haemopoiesis. Although there are no data available, physiological replacement
doses of exogenous T administered systemically are unlikely to raise intratesticular
testosterone to an extent that arrest of spermatogenesis induced by gonadotrophin
suppression will be prevented.
suppression of FSH is not a viable approach to achieve the contraceptive
target of azoospermia or severe oligozoospermia. Active or passive immunisation
against FSH has produced only modest suppression spermatogenesis in subhuman
primates. Males with inactivating mutations of FSH receptor
gene and transgenic mice with FSH beta knockout have either
only moderately impaired or normal spermatogenesis. These results are
consistent with current view that T and FSH act synergistically and may
substitute for each other at a variety of phases during
spermatogenesis. The physiological feedback inhibition by gonadal sex
steroids on hypothalamic GnRH and pituitary gonadotrophin secretion is
well established (Figure 1). The efficacy of female hormonal contraceptives
suggest that exogenous sex steroids may also be the most likely candidates
to achieve gonadotrophin suppression in men. Studies performed in the
1970s showed that either androgens alone or progestogens combined with
androgens were indeed effective in the suppression both of gonadotrophins
and spermatogenesis. Azoospermia was achieved in 40%-80% of normal Caucasian
men (with the remainder becoming severely oligozoospermic) without producing
unacceptable side effects or impairment of sexual function.
the prototype for further study, the androgen-only approach was chosen
because of the well-documented safety of T in many years of clinical use
in hypogonadal men, its economy as a single agent in achieving both gonadotrophin
maintaining sexual function simultaneously and the familiar albeit suboptimal
pharmacokinetics of available preparations.
1986 and 1990, the first ever study to examine the contraceptive efficacy
of induced azoospermia was carried out in 271 healthy volunteers from
10 centres in 7 countries using T enanthate 200 mg weekly.
A total of 157 azoospermic men entered the 12 month efficacy phase during
which continued weekly TE injections were the only form of contraception
used. One pregnancy occurred during 1486 months of exposure giving a Pearl
rate (pregnancy per 100 couples using method for one year) of 0.8 with
95% confidence intervals of 0.02-4.5. This affirmed the important principle
that suppression to azoospermia by hormonal method can confer
contraceptive efficacy comparable with female contraceptive and substantially
better than the condom.
azoospermia appears to be the logical target for optimally effective contraception,
a substantial minority of men remains oligozoospermic despite suppression
of gonadotrophins to undetectable levels. The fertility of these subjects
with residual spermatogenesis needs to be defined in order to assess the
overall contraceptive efficacy of the hormone approach. In the second
efficacy trial conducted by the WHO between 1990 to 1994,
349 out of 358 (98%) of healthy men from 15 centres in 9 countries were
suppressed to azoospermia or oligzoospermia (<5 million/mL) with TE
200 mg im weekly. They accumulated a total of 283.5 years of exposure,
during which there were 9 pregnancies. The risk of pregnancy was directly
correlated with sperm concentrations (Table 2). No pregnancies occurred
in 230 man-years of azoospermic exposure but the failure rate was high
at sperm densities above 3 million/mL. With sperm densities between 0.1
to 3.0 million /mL, 4 pregnancies occurred during 49.5 years of exposure
yielded a Pearl rate of 8.1 (2.2-20.70 per 100 person-years. The Pearl
rate of the method as a whole, including
all men with sperm densities below 3 million/mL (i.e. azoospermia to 3
million/mL), was 1.4 (0.4-3.7) per 100 person-years. This is comparable
typical first year failure rate of modern female reversible contraceptives
(OCP, injectables, medicated IUDs) and is superior to the condom (12 per
100 person-years), withdrawal (18 per 100 person-years) and periodic abstinence
100 person-years). Ninety-eight percent of Asian and 95% of Caucasian
men suppressed to 3 million/mL,
or less, indicating that the vast majority of men are able to achieve
this oligozoospermic threshold of contraceptive efficacy. These two trials
using a prototype regime established the important principle that hormonal
suppression of spermatogenesis can provide effective reversible contraception
for men and provided benchmark results on which future contraceptive studies
will be compared. The incidence of side effects (acne, weight gain, changes
in sex drive and mood)
was low apart from acne (29.3%) and the cumulative annual discontinuation
rate was 9.7%.
2. Mean (95% confidence intervals) pregnancy rates according to different
sperm concentrations suppressed by testosterone enanthate 200 mg im weekly
while couples are not using any other contraceptive methods. (Adapted
from WHO 1995).
and total cholesterol decreased by 18% and 6% respectively while haematocrit
increased by 6%. These effects reflect the high peak and markedly fluctuating
levels of T produced by weekly intramuscular injections of a supraphysiological
dose of T enanthate rather than an inherent feature of hormonal male contraception.
Moreover, the requirement for weekly painful injections
is impractical and unacceptable as a method of contraception. For these
reasons, improved methods or formulations for long-acting, stable delivery
of lower doses of testosterone are crucial for the continued development
implantation of T pellets subcutaneously is a popular method of physiological
androgen replacement in some countries. At doses of 600
to 800 mg, relatively stable but progressively declining levels of testosterone
within the physiological range can be maintained for 4-6 months. Following
a single administration of a supraphysiological dose of 1200 mg to normal
men, azoospermia can be induced with similar efficacy but apparently fewer
side effects than weekly intramuscular TE. Extrusion of
T pellets occurs in 8.5% of procedures in experienced hands. The feasibility
of maintaining spermatogenesis suppression and the acceptability of repeated
T implantation remain to be established.
undecanoate is an ester with a long aliphatic side chain that increases
its lipid solubility and facilitates absorption into intestinal lymphatics.
Because of the
improved oral bioavailability, T undecanoate was originally formulated
in arachis oil for orally-administered androgen replacement. Early attempts
to use oral
T undecanoate for male contraceptive spermatogenesis suppression, however,
were unsuccessful. Recently, T undecanoate has been re-formulated
in castor oil
for intramuscular injections. A single dose of 1000 mg T undecanoate achieving
a prolonged half-life of 33.9 days in hypogonadal men compared with 4.5
days for 250 mg of T enanthate. A multi-centre, contraceptive
dose-finding study using intramuscular T undecanoate (in tea seed oil)
500-1000 mg 4-6 weekly has recently been completed in China. T undecanoate
(TU) 1000 mg was found to induce reversible azoospermia in all 12 subjects
treated, whilst 11 of the twelve receiving TU 500 mg also achieved azoospermia.
(T buciclate), a long-acting ester of testosterone developed jointly by
the WHO and NICHD, USA, is formulated as an aqueous suspension of finely-milled
crystals (10-15 m particle size) and administered as intramuscular injections.
Both 600 and 1000 mg in single-dose injections raised plasma T gradually
in hypogonadal men into the low normal range and maintaining
stable concentrations for 16 and 20 weeks respectively (mean residence
A single dose of 1200 mg of testosterone buciclate produced azoospermia
in 3 out of 8 eugonadal men whose plasma testosterone remained within
the physiological range.
7-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen which is not 5-reduced but is aromatised to 7-methyl-oestradiol. In the castrated rat, MENT is four times more potent than T in maintaining ventral prostate and seminal vesicle weights but ten to twelve times more potent in maintaining muscle mass and in suppressing gonadotrophins. The favourable therapeutic index of MENT, presumably conferred by the lack of DHT stimulation of accessory sex glands, has also been confirmed in castrated monkeys. However MENT was also shown to be 10 times more potent than T in decreasing HDL- and total cholesterol. As a result of its increased potency and tissue selectivity, MENT has the potential advantage of being used at relatively low doses (one-tenth that of T) to suppress gonadotrophin secretion and maintain adult sexual functions and muscle mass without stimulating the prostate. The lower doses (and smaller mass of steroid) may also permit sufficient drug to be delivered by subdermal implants, skin patches or gels. This selective androgen receptor modulator (SARM) is currently being further investigated as a potential agent for androgen replacement and male contraception. Single intramuscular injection of 2-8 mg of micronized MENT to healthy men showed suppression of gonadotrophins without side effects. Subcutaneous implants containing 115 mg of MENT acetate (2 implants per subject) have recently been shown to maintain sexual behaviour and mood in hypogonadal men over a 6 week period.
(19-NT) or nandrolone is an anabolic steroid with not only a higher affinity
for the androgen receptor than T, but is also a potent progestogen. 19-NT
hexoxyphenylproprionate injected every 3 weeks for 3 months induced suppression
of gonadotrophins and testosterone and achieved azoospermia in 6 out of
12 volunteers without any symptoms of androgen deficiency.
If 19-NT can maintain essential androgen dependent functions without producing
undesirable metabolic, prostatic and behavioural effects with more prolonged
exposure, a 19-NT ester offers potential as a single agent anti-fertility
Combined hormonal male contraceptive
From the recent experience with various androgen-only regimens, it is likely that supraphysiological levels of testosterone are required to produce maximal suppression of spermatogenesis. The elevation in plasma T concentrations, especially with high post-injection peak levels produced by the suboptimal pharmacokinetics of current T esters such as enanthate or cypionate, are therefore likely to produce dose-dependent androgen-related side effects (vide supra). The theoretical possibility of increased risks for benign prostatic hyperplasia, prostatic carcinoma, cardiovascular disease in later years and behaviour disturbances (e.g. increased aggression) also raises concerns that cannot be easily allayed without long-term surveillance data. It seems prudent to consider an alternative approach in which the primary anti-gonadotrophic agent is non-androgenic while testosterone is deployed in lower physiological replacement doses.
Progestogen and androgen combination
Progestogens are potent inhibitors of gonadotrophin secretion in men and may also suppress spermatogenesis directly. They can act synergistically or additively with androgens thus permitting lower doses of each steroid to be combined with possibly greater efficacy than when either compound is used alone. Incorporating progestogens will also have the added advantage that any direct stimulatory effects exogenous androgens may have on spermatogenesis can be minimised or even antagonised. The synthetic third-generation progestogens derived from 19-NT (e.g. levonorgestrel, desogestrel, gestodene and norgestimate) are highly potent and effective in g doses in inhibiting ovulation in the combined female contraceptive pill. The comparatively low mass of drug required allows long-acting (2-5 years) subdermal implants such as Norplant (levonorgestrel, Wyeth) and Implanon (etonogestrel, Organon) to be successfully used for female contraception. Their value in male hormonal contraception remains to be established.
studies in 1970s an 1980s using depot medroxyprogesterone acetate (DMPA)
danazol, norethisterone acetate and levonorgestrel combined with sub-replacement
doses of testosterone established that these compounds can be used safely
for 12-24 months in normal men but spermatogenic suppression was variable.
Recent studies combining progestogens with higher doses of T have yielded
more encouraging results.
DPMA plus T
(200 or 100 mg) and T enanthate (250 or 100 mg) at monthly intervals for
4 months suppressed spermatogenesis to azoospermia in 19 out of 20 Indonesian
men. The high efficacy of hormone suppression in Indonesian
men was confirmed by a
larger 5centre study showing that DMPA, when combined with either 3-weekly 19-NT
or weekly T enanthate, was effective in inducing azoospermia in 97% of
subjects after 6 months. A single administration of 300
mg of DMPA combined with 800 mg of T implants induced azoospermia in 9
out of 10 Caucasian men. A single studies
showed that combination regimes of progestogen and androgen can be highly
Levonorgestrel plus T
levonorgestrel 500 g combined with intramuscular T enanthate 100 mg/week induced
azoospermia in 12 of 18 (67%) men. Reducing the dose of
levonorgestrel to 250 and 125 g daily produced similar results. Oral
desogestrel 150-300 g daily combined with intramuscular T enanthate
50-100 mg/week suppressed 18 of 24 (75%) men to azoospermia.
There is some indication that an optimised combination (e.g. desogestrel
300 g daily with T enanthate 50 mg weekly)
can induce azoospermia in all men, although the overall results from these
studies with small number of subjects suggest that progestogen-androgen
combinations may not be significantly more effective than testosterone
alone. The combination regimes also decreased HDL-cholesterol indicating
that 19-NT-derived oral progestogens exert significant effects of their
own on lipid metabolism in men independent of
CPA plus T
acetate is a synthetic steroid with both anti-androgenic and progestational
properties. It has been used in Europe for the treatment of hirsuitism
(Dianette, Schering) and prostate cancer. Recent studies showed that oral
cyproterone acetate is highly effective in suppressing spermatogenesis
to azoospermia in nearly all subjects in a dose-dependent manner (12.5
to 100 mg daily) when supplemented by intramuscular T enanthate.
No changes in lipids but a small decrease in haematocrit was observed.
The anti-androgenic properties of cyproterone acetate may account for
the superior results of this combination compared to other combinations
or androgens alone. Clinical trials of this combination are planned.
GnRH analogues and androgens
steroids are unlikely to be entirely free from side effects due to the
widespread distribution of their receptors and the broad range of physiological
actions in many non-reproductive tissues. Abolition of gonadotrophin secretion
can be achieved
via blockade of GnRH action on the GnRH receptors which are virtually
exclusively expressed in the anterior pituitary gonadotrophs only. This
unique specificity of action confined to the pituitary-gonadal axis and
offers the prospect of hormonal male contraception with freedom from non-reproductive
administration of superactive agonistic analogues of the natural GnRH decapeptide
initially stimulates gonadotrophins followed by down-regulation of the
GnRH receptors. Long-acting depot preparations of GnRH agonists have been
developed for use in the treatment of prostate cancer, endometriosis,
fibroids, precocious puberty and IVF. The potential of GnRH agonists (with
T replacement) to reduce
sperm production has been explored in 12 clinical studies.
Only 23% of
subjects achieved azoospermia and there was evidence that this modest
efficacy can be further blunted by the simultaneous use of exogenous androgen
replacement. Inadequate doses of the agonists and persistence of FSH are
two possible reasons for their relative ineffectiveness. GnRH agonists
have virtually been abandoned in the last decade as a potential candidate
for male contraception due to the availability of GnRH antagonists.
antagonists compete for the GnRH receptors with greater affinity and slower dissociation
rates than native GnRH. They are capable of reversibly suppressing
gonadotrophins more completely and rapidly than other compounds. GnRH
antagonists, with either simultaneous or delayed introduction of T replacement,
suppressed spermatogenesis to azoospermia in 35 out of 40 (88%) men within
6-8 weeks[39-41]. Local histamine reaction has, however, been
reported with some antagonists. Compared to most sex steroid-based regimens,
GnRH antagonists produce more
rapid and complete suppression of spermatogenesis. However, because of
biopotency, milligram amounts of these peptides are required to be administered
daily to achieve adequate gonadotrophin suppression in man. They are complex compounds
containing several synthetic amino acids and are currently expensive to
produce. For these reasons, current GnRH antagonists are
be developed as practical and economic contraceptive agents. In future,
the pursuit of
non-peptide orally active GnRH antagonists via novel technologies such
as conformational analysis of GnRH receptor-ligand interactions and combinatorial
chemistry may produce more suitable compounds for fertility regulation.
Heterogeneity of response to hormonal suppression of spermatogenesis
A striking finding from the studies described is the marked individual difference within and between population groups in the extent of spermatogenic arrest in response to gonadotrophin suppression. This is a key issue which bears on the general acceptance and wider applicability of hormonal male contraception.
Heterogeneity within population groups
Caucasian populations, sex steroids induce rates of azoospermia (responders)
ranging from 40% to 70% with the remainder becoming oligozoopermic (partial
responders). No major difference in physical or hormonal characteristics
or pharmacokinetics and pharmacodynamics between the responders and partial
responders have been identified. One possibility is the extent of residual
androgenic stimulation in the seminiferous tubules and this is supported
by evidence that partial responders exhibit higher 5-reductase activity
during treatment. Data in rats
showed that Leydig cells continue to secrete small amounts of T after
hypophysectomy and elimination of this persistent intratesticular
androgen action is important in achieving maximal spermatogenesis blockade.
Heterogeneity between population groups
of the surprising findings from the WHO trials was that Asian (Chinese, Indonesian
and Thai) men showed a consistently higher rate of spermatogenic suppression
(90%) when compared with European or American (74%) men.
Baseline anthropometric characteristics, biochemical, endocrine and semen
parameters or the levels of T and gonadotrophins during treatment do not
explain the inter-ethnic heterogeneity
in spermatogenic (and other tissue e.g. liver enzymes and lipid metabolism)
response to sex steroids. Caucasians and Chinese men residing
in the USA have higher levels of androgenic steroid precursors, which
serve as substrates for 5-reduced metabolites compared to Chinese in
China. There is however no inter-ethnic difference in 5-reductase
activity. This raises the interesting possibility of an environmental
or dietary origin to these population differences. Greater sensitivity
of LH to exogenous T infusion and lower daily sperm
production rates in Asians compared to Caucasians have
recently been reported.
Whether these differences are responsible for the heterogeneity in suppression
of spermatogenesis is currently unclear.
Serendipity has played its role in uncovering fertility suppressing side effects of compounds developed for other uses. The majority of these have not showed promise and indeed many have unacceptable levels of toxicity.
Testicular anti-spermatogenic agents
the plant pigment from cottonseed oil, was tested as a potential orally
active male contraceptive in over 9000 men in China in the 1970s. Because
of the high incidence of irreversible infertility and unacceptable side
effects such as
hypokalaemia, gossypol is no longer regarded as a candidate for male fertility
modest antifertility side effects of sulphapyridine has led to a search
for analogous but more potent compounds which are inhibitors of dihydrofolate
reductase. This revealed that the anti-malarial drug pyrimethamine at
high doses reversibly abolished fertility in male rats. It is hoped that
chemical modifications to the basic diaminopyrimidine structure would
improve the testicular selectivity of these compounds.
Post-testicular epididymal agents
and 6-chloro-6-deoxyglucose are both metabolised to
3-chlorolactaldehyde, the S-enantiomer of which has the same absolute
stereochemistry as R-glyceraldehyde,
the substrate for the glycolytic enzyme glyceraldehydes-3-phosphate dehydrogenase.
These compounds inhibit oxidative metabolism of glucose and other sugars
in the spermatozoa resulting in loss of sperm motility. Unfortunately,
the serious adverse effects of these compounds on the nervous system and
bone marrow precluded further development.
and tripdiolide are oxygenated diterpine epoxide compounds purified from
the plant Tryptergium wilfordii whose extract has been used as a traditional
Chinese medicine in the treatment of inflammatory and dermatological diseases.
animal studies showed triptolide induced infertility but immunosuppressive
effects were apparent at five to twelve times the antifertility dose.
Recent studies in the rat have demonstrated that triptolide exerts its
antifertility via post-testicular mechanisms on epididymal spermatozoa.
There is evidence that triptolide inhibits calcium influx into spermatozoa
which is required for the acrosome reaction and sperm hyperactivated motility.
Interestingly, nifedipine, the common anti-anginal and anti-hypertensive
drug which blocks L-type calcium channels
and calcium dependent ATPase in many tissues including spermatozoa has been
shown to reversibly impair in vitro rat sperm motility and in
in man. More specific blockade of sperm membrane calcium channels may
open new avenues for male contraception.
can accumulate in the seminal plasma and inhibit sperm motility directly
after ejaculation. The sperm-immobilising properties of ketoconazole in vitro
reside in the imidazole structure.
Substituted imidazole compounds are currently
being developed as inhibitors of sperm motility i.e. spermicides which
could be administered orally rather than topically.
Chronic mild testicular hyperthermia (1-2) can be produced by close apposition of the testes to the inguinal rings with the use of tight-fitting underpants or slings applied to the scrotum. Changes in semen parameters were observed in some[52,53] but not other studies. The inconsistent suppression of spermatogenesis and sperm quality produced by induced scrotal hyperthermia is unlikely to provide effective contraception.
the last decade, research in hormonal male contraception has firmly established
the principle that suppression of spermatogenesis by exogenous sex steroids
can offer effective and reversible contraception. T combined with progestogens
appears to be the most likely approach for product development initially.
GnRH antagonists and T, though highly effective, remain for the moment
impractical and expensive. The main obstacles are the current lack of
satisfactory androgen formulations and the incomplete suppression of spermatogenesis
in a significant minority of men. New androgens with improved pharmacokinetics
(stable blood levels and long duration) and more selective biological
actions (preferential action on pituitary, CNS and muscle over testis,
prostate and liver) are being actively sought to overcome these hurdles.
With the recent entry of the pharmaceutical industry into this area, it
is anticipated that hormonal male contraceptive products for clinical
use will become imminently available. This should encourage renewed efforts
in basic research to improve understanding of molecular regulation of
spermatogenesis and epididymal function so that novel antifertility agents
with more specific actions on the post-meiotic or post-testicular targets
can be identified. New pharmacological methods together with improved
condoms and methods of vas
occlusion should offer men increased choice and ample opportunities to
continue to share the responsibility of family planning in the new millennium.
Wrigley EA. Population and History. London: Weidenfeld & Nicolson;
1969. p 188.
to: Dr W. Morton Hair, now in MRC Reproductive Biology Unit, Centre for
Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9ET, U.K.