Administration of luteinizing hormone (LH) (or human chorionic gonadotropin) and follicle-stimulating hormone (FSH) is very effective in the treatment of male infertility due to hypogonadotropic hypogonadism. Although controversial, off-label clomiphene citrate, an antiestrogen, may also be effective by elevating gonadotropin levels.

Though androgens are absolutely essential for spermatogenesis and therefore male fertility, exogenous testosterone therapy has been found to be ineffective in benefiting men with low sperm count. This is thought to be because very high local levels of testosterone in the testes (concentrations in the seminiferous tubules are 20- to 100-fold greater than circulating levels) are required to mediate spermatogenesis, and exogenous testosterone therapy (which is administered systemically) cannot achieve these required high local concentrations (at least not without extremely supraphysiological dosages). Moreover, exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the pituitary gland, as seen in users of androgens/anabolic steroids (who often have partially or completely suppressed sperm production). This is because suppression of gonadotropin levels results in decreased testicular androgen production (causing diminished local concentrations in the testes) and because FSH is independently critical for spermatogenesis. In contrast to FSH, LH has little role in male fertility outside of inducing gonadal testosterone production.

Estrogen, at some concentration, has been found to be essential for male fertility/spermatogenesis. However, estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels. As such, clomiphene citrate (an antiestrogen) and aromatase inhibitors such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis.

Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men, including in men with severe oligospermia.

Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered.

Pre-testicular conditions can often be addressed by medical means or interventions.

Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved.

Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF.

Vitamin E helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility. A hormone-antioxidant combination may improve sperm count and motility. However there is only some low quality evidence from few small studies that oral antioxidants given to males in couples undergoing in vitro fertilisation for male factor or unexplained subfertility result in higher live birth rate. It is unclear if there are any adverse effects.

Pre- and post-testicular azoospermia are frequently correctible, while testicular azoospermia is usually permanent. In the former the cause of the azoospermia needs to be considered and it opens up possibilities to manage this situation directly. Thus men with azoospermia due to hyperprolactinemia may resume sperm production after treatment of hyperprolactinemia or men whose sperm production is suppressed by exogenous androgens are expected to produce sperm after cessation of androgen intake. In situations where the testes are normal but unstimulated, gonadotropin therapy can be expected to induce sperm production.

A major advancement in recent years has been the introduction of IVF with ICSI which allows successful fertilization even with immature sperm or sperm obtained directly from testicular tissue. IVF-ICSI allows for pregnancy in couples where the man has irreversible testicular azoospermia as long as it is possible to recover sperm material from the testes. Thus men with non-mosaic Klinefelter's syndrome have fathered children using IVF-ICSI. Pregnancies have been achieved in situations where azoospermia was associated with cryptorchism and sperm where obtained by testicular sperm extraction (TESE).

In men with posttesticular azoospermia a number of approaches are available. For obstructive azoospermia IVF-ICSI or surgery can be used and individual factors need to be considered for the choice of treatment. Medication may be helpful for retrograde ejaculation.

A problem for people with penile agenesis is the absence of a urinary outlet. Before genital metamorphosis, the urethra runs down the anal wall, to be pulled away by the genital tubercle during male development. Without male development this does not occur. The urethra can be surgically redirected to the rim of the anus immediately after birth to enable urination and avoid consequent internal irritation from urea concentrate. In such cases, the perineum may be left devoid of any genitalia, male or female.

A working penis transplant on to an agenetic patient has never been successful. Only one major penis graft was successfully completed. This occurred in China and the patient shortly rejected it on psychological grounds. However a full female or agenetic to male transplant is not yet facilitated to fulfil full reproductive functions.

On March 18, 2013, it was announced that Andrew Wardle, a British man born without a penis, was going to receive a pioneering surgery to create a penis for him. The surgeons hope to "fold a large flap of skin from his arm — complete with its blood vessels and nerves — into a tube to graft onto his pubic area." If the surgery goes well, the odds of starting a family are very good.

A number of treatments have become available to create a functioning vagina, yet in the absence of a uterus currently no surgery is available to make pregnancy possible. Standard approaches use vaginal dilators and/or surgery to develop a functioning vagina to allow for penetrative sexual intercourse. A number of surgical approaches have been used. In the McIndoe procedure, a skin graft is applied to form an artificial vagina. After the surgery, dilators are still necessary to prevent vaginal stenosis. The Vecchietti procedure has been shown to result in a vagina that is comparable to a normal vagina in patients. In the Vecchietti procedure, a small plastic “olive” is threaded against the vaginal area, and the threads are drawn through the vaginal skin, up through the abdomen and through the navel using laparoscopic surgery. There the threads are attached to a traction device. The operation takes about 45 minutes. The traction device is then tightened daily so the olive is pulled inwards and stretches the vagina by approximately 1 cm per day, creating a vagina approximately 7 cm deep in 7 days, although it can be more than this. Another approach is the use of an autotransplant of a resected sigmoid colon using laparoscopic surgery; results are reported to be very good with the transplant becoming a functional vagina.

Uterine transplantation has been performed in a number of people with MRKH, but the surgery is still in the experimental stage. Since ovaries are present, people with this condition can have genetic children through IVF with embryo transfer to a gestational carrier. Some also choose to adopt. In October 2014 it was reported that a month earlier a 36-year-old Swedish woman became the first person with a transplanted uterus to give birth to a healthy baby. She was born without a uterus, but had functioning ovaries. She and the father went through IVF to produce 11 embryos, which were then frozen. Doctors at the University of Gothenburg then performed the uterus transplant, the donor being a 61-year-old family friend. One of the frozen embryos was implanted a year after the transplant, and the baby boy was born prematurely at 31 weeks after the mother developed pre-eclampsia.

Promising research include the use of laboratory-grown structures, which are less subject to the complications of non-vaginal tissue, and may be grown using the person's own cells as a culture source. The recent development of engineered vaginas using the patient's own cells has resulted in fully functioning vaginas capable of menstruation and orgasm in a number of patients showing promise of fully correcting this condition in some of the sufferers.

Because hormone treatment rarely achieves average size, several surgical techniques similar to phalloplasty for penis enlargement have been devised and performed; but they are not generally considered successful enough to be widely adopted and are rarely performed in childhood.

In extreme cases of micropenis, there is barely any shaft, and the glans appears to sit almost on the pubic skin. From the 1960s until the late 1970s, it was common for sex reassignment and surgery to be recommended. This was especially likely if evidence suggested that response to additional testosterone and pubertal testosterone would be poor. With parental acceptance, the boy would be reassigned and renamed as a girl, and surgery performed to remove the testes and construct an artificial vagina. This was based on the now-questioned idea that gender identity was shaped entirely from socialization, and that a man with a small penis can find no acceptable place in society.

Johns Hopkins Hospital, the center most known for this approach, performed twelve such reassignments from 1960 to 1980, most notably that of David Reimer (whose penis was destroyed by a circumcision accident), overseen by John Money. By the mid-1990s, reassignment was less often offered, and all three premises had been challenged. Former subjects of such surgery, vocal about their dissatisfaction with the adult outcome, played a large part in discouraging this practice. Sexual reassignment is rarely performed today for severe micropenis (although the question of raising the boy as a girl is sometimes still discussed.) (See "History of intersex surgery" for a fuller discussion.)

A treatment option for micropenis is the insertion of a subcutaneous soft silicone implant under the penile skin. The procedure was developed by urologist James J. Elist.

Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or identify as the female gender, estrogens should be given instead. Surgical correction of the genitals in 46,XY males may be required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well.

Growth of the penis both before birth and during childhood and puberty is strongly influenced by testosterone and, to a lesser degree, the growth hormone. However, later endogenous hormones mainly have value in the treatment of micropenis caused by hormone deficiencies, such as hypopituitarism or hypogonadism.

Regardless of the cause of micropenis, if it is recognized in infancy, a brief course of testosterone is often prescribed (usually no more than 3 months). This usually induces a small amount of growth, confirming the likelihood of further growth at puberty, but rarely achieves normal size. No additional testosterone is given during childhood, to avoid unwanted virilization and bone maturation. (There is also some evidence that premature administration of testosterone can lead to reduced penis size in the adult.)

Testosterone treatment is resumed in adolescence only for boys with hypogonadism. Penile growth is completed at the end of puberty, similar to the completion of height growth, and provision of extra testosterone to post-pubertal adults produces little or no further growth.

In order to facilitate sexual intercourse, the main treatments are self-dilation methods (using intra-vaginal cylinders of increasing size) and surgical vaginoplasty to lengthen the vagina.

Self-dilation has a high success rate, estimated at 75%, and is usually the first-line treatment due to low surgical invasiveness. Overall, the complication rates are significantly lower with dilation than with vaginoplasty.

Surgery is indicated when there is inability or reluctance to perform self-dilation, or where it is performed but with failed result. One appropriate surgical variant is the "Vecchietti technique". In this procedure, an olive-shaped pressure device is pressed towards the potential vaginal space by a thread that goes through the skin, behind the urinary bladder and pubic bone and exits the skin in the hypogastrium, where it is attached to a plate that provides counter-traction. Vaginoplasty can also be performed using a skin graft or an intestinal graft. Traction vaginoplasty such as the "Vecchietti technique" seems to have the highest success rates both anatomically (99%) and functionally (96%), whereas skin graft procedures and intestinal procedures have the lowest successful outcomes (83–95%).

After vaginoplasty, available evidence suggests that continued self-dilation is needed to maintain patency in periods of coital inactivity.

Congenital anomalies like cryptorchidism, renal agenesis/dysplasia, musculoskeletal and cardiopulmonary anomalies are also common (>50% cases), hence evaluation of the patient for internal anomalies is mandatory.

Although aphallia can occur in any body type, it is considered a substantially more troublesome problem with those who have testes present, and has in the past sometimes been considered justification for assigning and rearing a genetically male infant as a girl. After the theory in the 1950s that gender as a social construct was purely nurture and so an individual child could be raised early on and into one gender or the other regardless of their genetics or brain chemistry. Intersex people generally advocate harshly against coercive genital reassignment however, and encourage infants to be raised choosing their own gender identity. The nurture theory has been largely abandoned and cases of trying to rear children this way have not proven to be successful transitions.

In newborn period or infancy, feminizing operations are recommended for treatment of penile agenesis, but after 2 years, as sexual identification of the patients has appeared, it is advised to perform masculinizing operations in order not to disturb the child psychologically.

Recent advances in surgical phalloplasty techniques have provided additional options for those still interested in pursuing surgery.

The first line of therapy after diagnosis typically involves the administration of the combined oral contraceptive pill, medroxyprogesterone acetate or a gonadotropin-releasing hormone agonist to suppress menstruation and thereby relieve pain. Surgically, cervical agenesis has historically been treated through hysterectomy (removal of the uterus) to relieve symptoms caused by hematocolpos (the accumulation of menstrual fluid in the vagina). Other surgical methods of management involve the creation of an anastomotic connection between the uterus and vagina by neovaginoplasty or recanalization of the cervix. Outcomes in these cases are generally poor, since the natural functions of the cervix—such as mucus production and providing a barrier against ascending infection—cannot be replicated. Furthermore, the success rate of uterovaginal anastomosis is less than 50% and most patients require multiple surgeries while many develop cervical stenotis. Despite this, several pregnancies have been reported in women with cervical agenesis who underwent surgical treatment.

Surgical intervention depends on the extent of the individual problem. With a didelphic uterus surgery is not usually recommended.

A uterine septum can be resected in a simple out-patient procedure that combines laparoscopy and hysteroscopy. This procedure greatly decreases the rate of miscarriage for women with this anomaly.

Individuals with CAVD can reproduce with the assistance of modern technology with a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI). However, as the risk of either cystic fibrosis or renal agenesis is likely to be higher in the children, genetic counseling is generally recommended.

People with either penile agenesis or testicular agenesis, but not both, usually continue as males throughout their lives. Historically, people with both penile and testicular agenesis were raised as females and eventually underwent sex reassignment surgery, despite having a normal 46,XY male karyotype and no female sexual characteristics. This practice was controversial, and many individuals decided to live as males again when they reached puberty or their early twenties. The New Zealand sexologist John Money was the principle theorist who argued that boys born without an "adequate" penis, or who lost their penis in an accident, should be raised as sex reassigned girls. The book "As Nature Made Him" chronicles the disastrous results of the application of Money's theories in the Bruce/Brenda case. The anatomy underlying the failure of these cases is not well understood. In most males, the development of the embryo into a female is prevented by Anti-Müllerian hormones. These hormones are commonly believed to be created in the testes, but they nevertheless still appear to be produced in male embryos lacking testes.

Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen in up to 20% of male infertility situations.

Poor semen quality is measured not only by the number of sperm a man produces but also by how effective the sperm is at fertilising an egg. The motility and shape of the sperm are important for this role. A man with poor semen quality will often present with fertility problems which is defined as a couple trying to conceive for over 1 year with no success. Diagnosis can be made from semen analysis, taking a sample of the man’s semen and running tests to count numbers and quality of the individual sperm.

Central to the cause of irreversible TDS are disruptions to early fetal testes development. This has both genetic, environmental, and lifestyle components, however the rapid increase in the incidence of the disorders associated with TDS in the last decades indicates that it is under a powerful environmental influence. The fetal origins of TDS are reinforced by the high incidence of TDS disorders found occurring together in one individual.

Aphallia is a congenital malformation in which the phallus (penis or clitoris) is absent. It is the female counterpart of penile agenesis and testicular agenesis. The word is derived from the Greek "a-" for "not", and "phallos" for "penis". It is classified as an intersex condition.

Müllerian agenesis or müllerian aplasia, Mayer–Rokitansky–Küster–Hauser syndrome, or vaginal agenesis is a congenital malformation characterized by a failure of the Müllerian duct to develop, resulting in a missing uterus and variable degrees of vaginal hypoplasia of its upper portion. Müllerian agenesis (including absence of the uterus, cervix and/or vagina) is the cause in 15% of cases of primary amenorrhoea. Because most of the vagina does not develop from the Müllerian duct, instead developing from the urogenital sinus along with the bladder and urethra, it is present even when the Müllerian duct is completely absent.

Because ovaries do not develop from the Müllerian ducts, affected women might have normal secondary sexual characteristics but are infertile due to the lack of a functional uterus. However, motherhood is possible through use of gestational surrogates. Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is hypothesized to be a result of autosomal dominant inheritance with incomplete penetrance and variable expressivity, which contributes to the complexity involved in identifying of the underlying mechanisms causing the condition. Because of the variance in inheritance, penetrance and expressivity patterns, MRKH is subdivided into two types: type 1, in which only the structures developing from the Müllerian duct are affected (the upper vagina, cervix, and uterus), and type 2, where the same structures are affected, but is characterized by the additional malformations of other body systems most often including the renal and skeletal systems. MRKH type 2 includes MURCS (Müllerian Renal Cervical Somite). The majority of MRKH syndrome cases are characterized as sporadic, but familial cases have provided evidence that, at least for some patients, MRKH is an inherited disorder. The underlying causes of MRKH syndrome is still being investigated, but several causative genes have been studied for their possible association with the syndrome. Most of these studies have served to rule-out genes as causative factors in MRKH, but thus far, only WNT4 has been associated with MRKH with hyperandrogenism.

The medical eponym honors August Franz Josef Karl Mayer (1787–1865), Carl Freiherr von Rokitansky (1804–1878), Hermann Küster (1879–1964), and Georges Andre Hauser (1921–2009).

Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), and infertility.

Leydig cell hypoplasia does not occur in biological females as they do not have either Leydig cells or testicles. However, the cause of the condition in males, luteinizing hormone insensitivity, does affect females, and because LH plays a role in the female reproductive system, it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation), infertility due to anovulation, and ovarian cysts.

A related condition is follicle-stimulating hormone (FSH) insensitivity, which presents with similar symptoms to those of Leydig cell hypoplasia but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in females and merely problems with fertility in males). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity.

Treatments vary based on the underlying condition. Key issues are problems of surgical correction if appropriate and oestrogen therapy if oestrogen levels are low. For those who do not plan to have biological children, treatment may be unnecessary if the underlying cause of the amenorrhoea is not threatening to their health. However, in the case of athletic amenorrhoea, deficiencies in estrogen and leptin often simultaneously result in bone loss, potentially leading to osteoporosis.

"Athletic" amenorrhoea which is part of the female athlete triad is treated by eating more and decreasing the amount and intensity of exercise. If the underlying cause is the athlete triad then a multidisciplinary treatment including monitoring from a physician, dietitian, and mental health counselor is recommended, along with support from family, friends, and coaches. Although oral contraceptives can causes menses to return, oral contraceptives should not be the initial treatment as they can mask the underlying problem and allow other effects of the eating disorder, like osteoporosis, continue to develop. Weight recovery, or increased rest does not always catalyze the return of a menses. Recommencement of ovulation suggests a dependency on a whole network of neurotransmitters and hormones, altered in response to the initial triggers of secondary amenorrhoea. To treat drug-induced amenorrhoea, stopping the medication on the advice of a doctor is a usual course of action.

Looking at Hypothalamic amenorrhoea, studies have provided that the administration of a selective serotonin reuptake inhibitor (SSRI) might correct abnormalities of Functional Hypothalamic Amenorrhoea (FHA) related to the condition of stress-related amenorrhoea. This involves the repair of the PI3K signaling pathway, which facilitates the integration of metabolic and neural signals regulating gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH). In other words, it regulates the neuronal activity and expression of neuropeptide systems that promote GnRH release. However, SSRI therapy represents a possible hormonal solution to just one hormonal condition of hypothalamic amenorrhoea. Furthermore, because the condition involves the inter workings of many different neurotransmitters, much research is still to be done on presenting hormonal treatment that would counteract the hormonal affects.

As for physiological treatments to hypothalamic amenorrhoea, injections of metreleptin (r-metHuLeptin) have been tested as treatment to oestrogen deficiency resulting from low gonadotropins and other neuroendocrine defects such as low concentrations of thyroid and IGF-1. R-metHuLeptin has appeared effective in restoring defects in the hypothalamic-pituitary-gonadal axis and improving reproductive, thyroid, and IGF hormones, as well as bone formation, thus curing the amenorrhoea and infertility. However, it has not proved effective in restoring of cortisol and adrenocorticotropin levels, or bone resorption.

About 10–15% of human couples are infertile, unable to conceive. In approximately in half of these cases, the underlying cause is related to the male. The underlying causative factors in the male infertility can be attributed to environmental toxins, systemic disorders such as, hypothalamic–pituitary disease, testicular cancers and germ-cell aplasia. Genetic factors including aneuploidies and single-gene mutations are also contributed to the male infertility. Patients suffering from nonobstructive azoospermia or oligozoospermia show microdeletions in the long arm of the Y chromosome and/or chromosomal abnormalities, each with the respective frequency of 9.7% and 13%. A large percentage of human male infertility is estimated to be caused by mutations in genes involved in primary or secondary spermatogenesis and sperm quality and function. Single-gene defects are the focus of most research carried out in this field.

NR5A1 mutations are associated with male infertility, suggesting the possibility that these mutations cause the infertility. However, it is possible that these mutations individually have no major effect and only contribute to the male infertility by collaboration with other contributors such as environmental factors and other genomics variants. Vice versa, existence of the other alleles could reduce the phenotypic effects of impaired NR5A1 proteins and attenuate the expression of abnormal phenotypes and manifest male infertility solely.

Congenital absence of the vas deferens (CAVD) is a condition in which the vasa deferentia reproductive organs, fail to form properly prior to birth. It may either be unilateral (CUAVD) or bilateral (CBAVD).

Although rare, this condition is often treatable with surgery. In most cases, the blind hemivagina is opened, and the fluid drained.

Although there is no cure for 13q deletion syndrome, symptoms can be managed, usually with the involvement of a neurologist, rehabilitation physician, occupational therapist, physiotherapist, psychotherapist, nutritionist, special education professional, and/or speech therapist. If the affected child's growth is particularly slow, growth hormone treatment can be used to augment growth. Plastic surgeries can repair cleft palates, and surgical repair or monitoring by a pediatric cardiologist can manage cardiac defects. Some skeletal, neurological, genitourinary, gastrointestinal, and ophthalmic abnormalities can be definitively treated with surgery. Endocrine abnormalities can often be managed medically. Special educators, speech and occupational therapists, and physiotherapists can help a child develop skills in and out of school.