Hormonal and genetic control of testicular descent

Cryptorchidism has the potential to affect the health of the human male. Although it is often considered a mild malformation, it represents the best-characterized risk factor for reduced fertility and testicular cancer. The aetiology of cryptorchidism remains, for the most part, unknown and cryptorchidism itself might be considered a complex disease. This reflects the intricate mechanisms regulating testicular development and descent from intra-abdominal location into the bottom of the scrotum, involving different anatomical and hormonal factors. Major actors of testicular descent are the Leydig cell-derived hormones testosterone and insulin-like factor 3, even if other factors may play a role. Although considerable evidence exists in animals to support a genetic cause, the genetic contribution to human cryptorchidism is only recently being elucidated. Environmental factors might also contribute to the aetiology of cryptorchidism and its increased incidence in recent years. Mutations in the gene for insulin-like factor 3 and its receptor and in the androgen receptor gene explain a minority of cases of cryptorchidism, but research on genetic polymorphisms that may also influence susceptibility to endocrine disruptors is shedding light on this field.     

Hormonal situation on parturition, early puerperium, and lactation (author's transl)]

Variations of the 17-beta oestradiol, progesterone, and prolactin levels in the serum were studied in the context of ten spontaneous parturitions. All cases were investigated within the first five puerperal days, but in five cases additional checks were undertaken over the first four weeks of the puerperium. Milk secretion was measured, as well. The oestradiol and progesterone titres were found to remain below the level common toward the end of pregnancy. They dropped rapidly after parturition and remained low throughout the puerperium. Prolactin underwent slight variation on parturition, but it actually stayed at the high level measurable at full term. Parturition was followed by brief temporary rise and, again, by decline, but values remained above those of non-pregnant women throughout puerperium. Milk production increased gradually over the first five days and remained similarly high throughout several weeks, accompanied by accordingly high prolactin levels. No absolute correlation was found to exist between the extent of lactation and the prolactin level. The presence of a relationship between oestradiol and progesterone levels, on the one hand, and lactation, on the other, cannot be assumed with probability.     

Hormonal and genetic control of germ cell apoptosis in the testis

Programmed cell death is an evolutionarily conserved cell death process that plays a major role during normal development and homeostasis. In many cases, the ordered execution of this internal death programme leads to typical morphological and biochemical changes that have been termed apoptosis. The crucial role of this mode of cell death in the pathogenesis of diverse human diseases including cancer, acquired immunodeficiency syndrome, neurodegeneratives disorders, atherosclerosis and cardiomyopathy is now supported by a wealth of data. In adult mammals, including humans, germ cell death is conspicuous during normal spermatogenesis and plays a pivotal role in sperm output. Withdrawal of gonadotrophins and testosterone further enhances the degeneration of germ cells in the testis. The availability of a quantitative method for analysing the testicular DNA fragmentation and in situ methods to localize specific germ cells undergoing apoptosis, either spontaneously or in response to a variety of death triggering signals, opens new avenues in the understanding of the significance of germ cell apoptosis during normal and abnormal states of spermatogenesis. A growing body of evidence demonstrates that both spontaneous (during normal spermatogenesis) and accelerated germ cell death triggered by deprivation of the gonadotrophic support or moderately increased scrotal temperature in adult rats occur almost exclusively via apoptosis. Although there has been spectacular progress in the understanding of the molecular mechanisms of apoptosis in various systems other than spermatogenesis, elucidation of the biochemical and molecular mechanisms by which germ cell apoptosis is regulated has only just begun. It is likely that germ cell apoptosis is controlled in a cell-type specific fashion, but the basic elements of the death machinery may be universal. In addition, there is increasing evidence that homozygous disruption of a number of genes in mice results in infertility through accelerated germ cell apoptosis. Manipulation of spermatogenesis by survival factor(s) deprivation or increases in extrinsic death signals in loss-of-function or gain-of-function mouse models provides a basis for further attempts to define the intrinsic regulation of various death-related genes by external death signals. Such information is crucial for effective management of male factor infertility as well as more targeted approaches to male contraception.     

Hormonal control of the secretory immune system of the human uterine cervix

A quantitative immunohistological study of IgA-containing plasma cells in the human uterine cervix has shown that the number of such cells increases during the late secretory phase of the menstrual cycle but decreases in the early secretory phase of the cycle, in pregnancy, in cystic glandular hyperplasia of the endometrium and after the menopause. These results are interpreted as indicating that progesterone causes an increased plasma cell localisation in the cervix whilst oestrogens cause a decrease: it is suggested that this reflects hormonal control of a receptor mechanism and that this receptor can also be blocked by high levels of LH or hCG.The number of cervical epithelial cells containing secretory component (SC) is increased in the late secretory phase of the menstrual cycle, in users of contraceptive pills and in pregnancy. It is suggested that progesterone acts to increase the intra-epithelial content of SC and that no other hormonal factor need be involved.     

Physiology of lactation and factors affecting lactation

Breast-feeding may be considered an ancient yet modern phenomenon. Despite trends toward bottle feeding in the 1950s and 1960s, the value of breast feeding is being rediscovered, because it is nutritionally ideal and now fashionable to connect pregnancy and the puerperium with being as "natural" as possible. Nursing normally begins shortly after delivery. This enhances the mother-infant relationship in terms of bonding, and it also stimulates mature milk production. The duration of the nursing period is widely variable, even within cultures. Dietary precautions should ensure adequate maternal dietary intake during breast feeding and should include avoidance of nonessential medications. With proper care and concern, nursing must be considered the ideal form of nutrition for the newborn human.     

Hormonal contraception

When used correctly, hormonal contraception--oral contraceptives (OCs), injectable progestins, and subdermal implants, in particular--can offer the most effective reversible method of pregnancy prevention available. The availability of OCs with lower hormonal dosages and more careful screening of OC acceptors have apparently eliminated the increased risk of vascular disease documented among OC users in the 1970s. Lower-dose OCs also have a lesser adverse effect on lipids and glucose metabolism. In fact, use of low-dose OCs may have a beneficial impact from the standpoint of lipid changes. The association between OC use and breast cancer remains unresolved, although recent studies suggest that the apparently increased risk among women 20-44 years of age is followed by a decreased risk among nulliparous women 45-54 years old. The reduced androgenic potency of 3 new progestins--gestodene, desogestrel, and norgestimate--is expected to increase further the safety of OC use and reduce side effects such as withdrawal bleeding. The most important recent development in the field of hormonal contraception has been the use of antiprogesterones such as RU-486. These agents not only have numerous therapeutic uses (e.g., as abortifacients or inhibitors of ovulation), but also offer insight into the mechanisms of steroid hormone action. Less productive has been research into steroidal contraception for men, although early trials of weekly injections with long-acting androgens have produced promising results.     

Hormonal contraception

Hormonal contraceptives have been a part of clinical practice for more than 40 years, and family planning programs, based largely on contraceptive provision, are regarded as one of the most successful public health interventions of the 20th century. Thus, discussion of family planning issues and contraceptive considerations has become an integral component of women's health care and one of the benchmarks of the traditional annual well-women visit. In terms of cost-effectiveness, prevention of unplanned pregnancies through contraceptive use has repeatedly been shown to be a highly cost-effective use of health care dollars. Options for effective hormonal contraception have expanded tremendously and include a variety of delivery options, including the pills both in traditional 21/7 format, and more recently in a 24/4 format, as well as a vaginal ring, a skin patch, implants, and the hormonally medicated intrauterine device. Importantly, the overall risks associated with hormonal contraceptives have been reduced as compared with older formulations, even for women with medical conditions. Many modern hormonal contraceptives also offer valuable noncontraceptive benefits. To help clinical decision making, a number of evidence-based guides have been published, and the American College of Obstetricians and Gynecologists has recently updated their practice bulletin on contraception use in women with medical conditions. In general, clinical protocols for provision of hormonal contraceptives have been streamlined, and unnecessary practices, tests, and procedures are identified and discouraged. In this review, we will summarize both technical and programmatic aspects of hormonal contraceptive use, and methods are discussed in order of efficacy from highest to lowest.