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.

Most cases of vaginal hypoplasia associated with CAIS can be corrected using non-surgical pressure methods. The elastic nature of vaginal tissue, as demonstrated by its ability to accommodate the differences in size between a tampon, a penis, and a baby's head, make dilation possible even in cases when the vaginal depth is significantly compromised. Treatment compliance is thought to be critical to achieve satisfactory results. Dilation can also be achieved via the Vecchietti procedure, which stretches vaginal tissues into a functional vagina using a traction device that is anchored to the abdominal wall, subperitoneal sutures, and a mold that is placed against the vaginal dimple. Vaginal stretching occurs by increasing the tension on the sutures, which is performed daily. The non-operative pressure dilation method is currently recommended as the first choice, since it is non-invasive, and highly successful. Vaginal dilation should not be performed before puberty.

While it is recommended that women with CAIS eventually undergo gonadectomy to mitigate cancer risk, there are differing opinions regarding the necessity and timing of gonadectomy. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. However, only three cases of malignant germ cell tumors in prepubescent girls with CAIS have been reported in the last 100 years. The youngest of these girls was 14 years old. If gonadectomy is performed early, then puberty must be artificially induced using gradually increasing doses of estrogen. If gonadectomy is performed late, then puberty will occur on its own, due to the aromatization of testosterone into estrogen. At least one organization, the Australasian Paediatric Endocrine Group, classifies the cancer risk associated with CAIS as low enough to recommend against gonadectomy, although it warns that the cancer risk is still elevated above the general population, and that ongoing cancer monitoring is essential. Some choose to perform gonadectomy if and when inguinal hernia presents. Estrogen replacement therapy is critical to minimize bone mineral density deficiencies later in life.

XX males are sterile due to low or no sperm content and there is currently no treatment to address this infertility. Genital ambiguities, while not necessary to treat for medical reasons, can be treated through the use of hormonal therapy, surgery, or both. Since XX male syndrome is variable in its presentation, the specifics of treatment varies widely as well. In some cases gonadal surgery can be performed to remove partial or whole female genitalia. This may be followed by plastic and reconstructive surgery to make the individual appear more externally male. Conversely, the individual may wish to become more feminine and feminizing genitoplasty can be performed to make the ambiguous genitalia appear more female. Hormonal therapy may also aid in making an individual appear more male or female.

Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.

Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), a course of ovarian stimulating medication maybe used. The physician or WHNP may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor or WHNP introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.

If conservative medical treatments fail to achieve a full term pregnancy, the physician or WHNP may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.

ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.

Other medical techniques are e.g. tuboplasty, assisted hatching, and Preimplantation genetic diagnosis.

Medications for PCOS include oral contraceptives and metformin. The oral contraceptives increase sex hormone binding globulin production, which increases binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods. Metformin is a drug commonly used in type 2 diabetes to reduce insulin resistance, and is used off label (in the UK, US, AU and EU) to treat insulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and return to normal ovulation. Spironolactone can be used for its antiandrogenic effects, and the topical cream eflornithine can be used to reduce facial hair. A newer insulin resistance drug class, the thiazolidinediones (glitazones), have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile. The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin when other therapy has failed to produce results. Metformin may not be effective in every type of PCOS, and therefore there is some disagreement about whether it should be used as a general first line therapy. The use of statins in the management of underlying metabolic syndrome remains unclear.

It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprolide. Metformin improves the efficacy of fertility treatment when used in combination with clomiphene. Metformin is thought to be safe to use during pregnancy (pregnancy category B in the US). A review in 2014 concluded that the use of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester.

Most people develop symptoms of estrogen deficiency, including vasomotor flushes and vaginal dryness, both of which respond to hormone replacement therapy. There are several contraindications of estrogen supplement, including smokers over 35 years of age, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of thromboemboli events.

Women younger than 40 year with primary ovarian insufficiency benefit from physiologic replacement of hormones. Most authorities recommend that this hormone replacement continue until age 50 years, the normal age of menopause. The leading hormone replacement regimen recommended involves the administration of estradiol daily by either skin patch or vaginal ring. This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy. To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of medroxyprogesterone acetate per day for days one through 12 of each calendar month. This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed primary ovarian insufficiency conceive a pregnancy after the diagnosis without medical intervention.

The transdermal estradiol patch is commonly recommended due to several advantages. It provides the replacement by steady infusion rather than by bolus when taking daily pills. It also avoids the first-pass effect in the liver.

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.

When appropriate (e.g., in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism. Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.

Other drugs with anti-androgen effects include flutamide, and spironolactone, which can give some improvement in hirsutism. Metformin can reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other features such as insulin resistance, diabetes, or obesity that should also benefit from metformin. Eflornithine (Vaniqa) is a drug that is applied to the skin in cream form, and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face. 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used; they work by blocking the conversion of testosterone to dihydrotestosterone (the latter of which responsible for most hair growth alterations and androgenic acne).

Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals), the reduction in hair growth may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking or shaving. Individuals vary in their response to different therapies. It is usually worth trying other drug treatments if one does not work, but drug treatments do not work well for all individuals.

Hormone replacement therapy with estrogen may be used to treat symptoms of hypoestrogenism in females with the condition. There are currently no known treatments for the infertility caused by the condition in either sex.

Due to its mild presentation, MAIS often goes unnoticed and untreated. Management of MAIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Treatment includes surgical correction of mild gynecomastia, minor hypospadias repair, and testosterone supplementation. Supraphysiological doses of testosterone have been shown to correct diminished secondary sexual characteristics in men with MAIS, as well as to reverse infertility due to low sperm count. As is the case with PAIS, men with MAIS will experience side effects from androgen therapy (such as the suppression of the hypothalamic-pituitary-gonadal axis) at a higher dosage than unaffected men. Careful monitoring is required to ensure the safety and efficacy of treatment. Regular breast and prostate examinations may be necessary due to comorbid association with breast and prostate cancers.

Treatment takes place within the context of infertility management and needs also to consider the fecundity of the female partner. Thus the choices can be complex.

In a number of situations direct medical or surgical intervention can improve the sperm concentration, examples are use of FSH in men with pituitary hypogonadism, antibiotics in case of infections, or operative corrections of a hydrocele, varicocele, or vas deferens obstruction.

In most cases of oligospermia including its idiopathic form there is no direct medical or surgical intervention agreed to be effective. Empirically many medical approaches have been tried including clomiphene citrate, tamoxifen, HMG, FSH, HCG, testosterone, Vitamin E, Vitamin C, anti-oxidants, carnitine, acetyl-L-carnitine, zinc, high-protein diets. In a number of pilot studies some positive results have been obtained. Clomiphene citrate has been used with modest success. The combination of tamoxifen plus testosterone was reported to improve the sperm situation.

The use of carnitine showed some promise in a controlled trial in selected cases of male infertility improving sperm quality and further studies are needed.

In many situations, intrauterine inseminations are performed with success. In more severe cases IVF, or IVF - ICSI is done and is often the best option, specifically if time is a factor or fertility problems coexist on the female side.

The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men including severe oligospermia.

Research into globozoospermia is aimed at improving understanding of its cause and developing treatment options.

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by "AR" gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

Treatment of hyperandrogenism varies with the underlying condition that causes it. As a hormonal symptom of polycystic ovary syndrome, menopause, and other endocrine disorders, it is primarily treated as a symptom of these disorders. Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to control the androgen levels in the patient's body. For Hyperandrogenism caused by Late-Onset Congenital Adrenal Hyperplasia (CAH), treatment is primarily focused on providing the patient with Glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the swelling of the Adrenal Glands. Oestrogen-based oral contraceptives are used to treat both CAH and PCOS caused hyperandrogenism. These hormonal treatments have been found to reduce the androgen excess and suppress adrenal androgen production and cause a significant decrease in hirsutism.

Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60-100% reporting an improvement in hirsutism. Androgenic alopecia however, does not show a significant improvement with hormonal treatments and requires other treatments, such as hair transplantation.

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.

Variable success rate with treatment, very few controlled studies, mostly case reports. Treatment success strongly tends to diminish with age and degree of elevation of FSH.

- Donor oocyte. Oocyte donation is the most successful method for producing pregnancy in perimenopausal women. In the UK the use of donor oocytes after natural menopause is controversial. A 1995 study reported that women age fifty or higher experience similar pregnancy rates after oocyte donation as younger women. They are at equal risk for multiple gestation as younger women. In addition, antenatal complications were experienced by the majority of patients, and that high risk obstetric surveillance and care is vital.

- Natural or Mini-IVF, but without the use of hCG to trigger ovulation, instead the GnRH agonist Synarel (nafarelin acetate) in a diluted form is taken as a nasal spray to trigger ovulation. Human chorionic gonadotropin (hCG) has a long half life and may stimulate (luteinize) small follicles prematurely and cause them to become cysts. Whereas nafarelin acetate in a nasal spray induces a short lived LH surge that is high enough to induce ovulation in large follicles, but too short lived to adversely affect small follicles. This increases the likelihood of the small follicles and oocytes therein developing normally for upcoming cycles and also allows the woman to cycle without taking a break and consequently increases the probability of conception in poor ovarian reserve women and advanced reproductive aged women.

- Pretreatment with 50 mcg ethinylestradiol three times a day for two weeks, followed by recombinant FSH 200 IU/day subcutaneously. Ethinylestradiol treatment was maintained during FSH stimulation. When at least one follicle reached 18mm in diameter and serum estradiol was greater or equal to 150 pg/ML ovulation was induced with an intramuscular injection of 10,000 IU of hCG (human chorionic gonadotropin hormone). For luteal phase support 5,000 IU of hCG was administered every 72 hours. Out of 25 patients 8 ovulated and 4 became pregnant. In the control group there were no ovulations. The patients ranged in age between 24 and 39 years with an average age of 32.7. All women had amenorrhea for at least 6 months (average 16.75 months) and FSH levels greater or equal than 40 mIU/mL (average FSH 68 mIU/ML). The researchers believe this protocol would work for women in early post menopause as well.

- Ethinylestradiol or other synthetic estrogens along with luteal phase progesterone (twice daily 200 mg vaginal suppositories) and estradiol support. Ethinylestradiol lowers high FSH levels which then, it is theorized, up regulates FSH receptor sites and restores sensitivity to FSH. Ethinylestradiol also has the advantage that it does not interfere with the measurement of serum levels of endogenous estradiol. During the luteal phase the FSH levels should be kept low for subsequent cycles, thus the phase is supplemented with 4 mg oral estradiol. Since conception may have occurred estradiol is used instead of the synthetic ethinylestradiol.

- Cyclical hormone replacement therapy.

- The following protocols have shown promise: high dose gonadoropins, flare up GnRH-a protocol (standard or microdose), stop protocols, short protocol, natural cycle or modified natural cycle and low dose hCG during the beginning of the stimulation protocol.

- Gonadotropin-releasing hormone agonist/antagonist conversion with estrogen priming (AACEP) protocol. Fisch, Keskintepe and Sher report 35% (14 out of 40) ongoing gestation in women with elevated FSH levels (all women had prior IVF and poor quality embryos); among women aged 41–42 the ongoing gestation rate was 19% (5 out of 26).

- DHEA: Recent clinical trial by the Center for Human Reproduction in New York showed significant effectiveness. Leonidas and Eudoxia Mamas report six cases of premature ovarian failure. After two to six months of treatment with DHEA (Two 25 mg capsules daily in five cases and three 25 mg capsules daily in one case.) all women conceived. One delivered via C-section, one aborted at 7 weeks and the remaining four were reported at 11 to 27 weeks gestation. Ages were from 37 to 40. FSH levels were from 30 to 112 mIU/mL. Ammenorhea ranged from 9 to 13 months. In addition, there is strong evidence that continuous micronized DHEA 25 mg TID reduces miscarriage and aneuploidy rates, especially above age 35.

- Glucocorticoid therapy. A recent (2007) randomized double blind study done in Egypt reported a statistically significant theurapeutic effect with dexamethasone pretreatment. Fifty-eight women with idiopathic premature ovarian failure and normal karyotype were divided into two groups of twenty-nine. The control group received placebo for twenty-eight days and then GnRH agonists plus gonadotropin therapy (hMG). The treatment group received dexamethasone for twenty-eight days (6 mg/ day) and then GnRH agonists plus gonadotropin therapy (hMG). (In both groups after the first twenty-eight days, and concurrent with the GnRH agonist treatment, the placebo or dexamethasone was gradually tapered off over ten days.) The treatment group had six ovulations and two pregnancies (p value of .02). The control group had three ovulations and no pregnancies.

- A combined pentoxifylline-tocopherol treatment has been reported effective in improving uterine parameters in women with POF undergoing IVF with donor oocytes (IVF-OD). Three women with uterine hormonoresistance despite high estradiol (E2) plasma levels received treatment with 800 mg pentoxifylline and 1000 IU of vitamin E for at least nine months. Three frozen-thawed embryo transfers (ETs) resulted in two viable pregnancies. Mean endometrial thickness increased from 4.9 mm (with thin uterine crosses) to 7.4 mm with nice uterine crosses. This treatment protocol has also reversed some cases of iatrogenic POF caused by full body radiation treatment.

Males and females may be treated with hormone replacement therapy (i.e., with androgens and estrogens, respectively), which will result in normal sexual development and resolve most symptoms. In the case of 46,XY (genetically male) individuals who are phenotypically female and/or identify as the female gender, they should be treated with estrogens instead. Removal of the undescended testes should be performed in 46,XY females to prevent their malignant degeneration, whereas in 46,XY males surgical correction of the genitals is generally required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well. Namely in genetic females presenting with ovarian cysts, GnRH analogues may be used to control high FSH and LH levels if they are unresponsive to estrogens.

The treatment of anovulation is termed ovulation induction and is usually quite efficient. The main treatments are clomifene citrate and gonadotropins.

Clomifene citrate (or clomid) is the medication which is most commonly used to treat anovulation. It is a selective estrogen-receptor modulator, affecting the hypothalamic–pituitary–gonadal axis to respond as if there was an estrogen deficit in the body, in effect increasing the production of gonadotrophins. It is relatively easy and convenient to use. Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on gonadotrophin production. It may also result in direct stimulation of the hypothalamic-pituitary axis. It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes.

The standard dosage for first-time takers is 50 or 100 mg of clomifene per day for five consecutive days, starting early in the menstrual cycle, usually on the third to fifth day counting from the beginning of the menstrual period. In case of amenorrhea, a period can be induced by intake of an oral progestin for 10 days. In absence of success, the dosage can be increased in subsequent cycles with increments of 50 mg. However, at a dosage of 200 mg, further increments are unlikely to increase pregnancy chances.

Potential methods in unexplained infertility include oral ovarian stimulation agents (such as clomifene citrate, anastrozole or letrozole) as well as intrauterine insemination (IUI), intracervical insemination (ICI) and in vitro fertilization (IVF).

In women who have not had previous treatment, ovarian stimulation combined with IUI achieves approximately the same live birth rate as IVF. On the other hand, in women who have had previous unsuccessful treatment, IVF achieves a live birth rate approximately 2-3 times greater than ovarian stimulation combined with IUI.

IUI and ICI has higher pregnancy rates when combined with ovarian stimulation in couples with unexplained infertility, for IUI being 13% unstimulated and 15% stimulated, and for ICI being 8% unstimulated and 15% stimulated. However, the rate of twin birth increases substantially with IUI or ICI combined with ovarian stimulation, for IUI being 6% unstimulated and 23% stimulated, and for ICI being 6% unstimulated and 23% stimulated.

According to NICE guidelines, oral ovarian stimulation agents should not be given to women with unexplained infertility. Rather, it is recommended that in vitro fertilization should be offered to women with unexplained infertility when they have not conceived after 2 years of regular unprotected sexual intercourse. IVF avails for embryo transfer of the appropriate number of embryos to give good chances of pregnancy with minimal risk of multiple birth.

A review of randomized studies came to the result that IVF in couples with a high chance of natural conception, as compared to IUI/ICI with or without ovarian stimulation, was "more" effective in three studies and "less" effective in two studies.

There is no evidence for an increased risk of ovarian hyperstimulation syndrome (OHSS) with IVF when compared with ovarian stimulation combined with IUI.

Treatment of HH is usually with hormone replacement therapy, consisting of androgen and estrogen administration in males and females, respectively.

Achieving a pregnancy naturally may be a challenge if the male suffers from a low sperm count. However, chances are good if the female partner is fertile; many couples with this problem have been successful. Prognosis is more limited if there is a combination of factors that include sperm dysfunction and reduced ovarian reserve.